Search PubMed⌕ Search

Biomedical subjects

H Kazemi

Publications and source records attributed to H Kazemi.

At least 73 records · Page 4Linked to original sources

Effect of furosemide on cerebrospinal fluid composition.

Electrolyte composition of the cerebral spinal fluid (CSF) is important in central respiratory drive. The relationship between [Cl-] and [HCO3-] is of particular interest in maintenance of electrolyte balance. Therefore, the effect of furosemide, an inhibitor of sodium-coupled chloride transport, on CSF electrolyte homeostasis was studied under conditions of normocapnia and hypercapnia in anesthetized dogs. The drug was given intravenously (IV) or in the lateral cerebral ventricles (CV). With normocapnia, there was no change in CSF or arterial PCO2, pH, [K+], [Cl-], or [HCO3-], while CSF [NA+] decreased 1.7 mM in dogs receiving IV furosemide. With 5% CO2 breathing and IV furosemide, CSF PCO2, pH, [K+], [Cl-], and [HCO3-] changed as has been reported for 5% CO2 breathing alone. 5% CO2 and CV furosemide, however, led to a greater reduction in CSF [Cl-] and no change in CSF [HCO3-]. Thus CV furosemide alters the CSF [Cl-] and [HCO3-] in hypercapnia, suggesting that sodium-coupled chloride transport plays a role in regulation of CSF acid-base homeostasis.

Acid-Base Equilibrium↗

Respiratory disease in tungsten carbide production workers.

We carried out a medical and environmental survey to evaluate respiratory disease at two tungsten carbide (TC) production plants. The study population of 290 subjects (19.2 percent of the total work force) was chosen to focus on those with the greatest potential exposures to cobalt, a binding agent which is probably the cause of interstitial fibrosis and airways disease in TC workers. We found peak air concentrations of cobalt exceeding 500 micrograms/m3 during many major steps in TC production. Nine subjects at plant A and two at plant B had interstitial infiltrates. Two of these nine from plant A had restriction (total lung capacity less than 80 percent of predicted). A lung biopsy specimen in one showed interstitial fibrosis. Two nonsmokers at plant A and one nonsmoker at plant B had obstructive defects. These results suggest that interstitial and obstructive lung disease occur in TC workers in association with elevated peak air concentrations of cobalt.

Adult↗

Movement of CO2 and HCO-3 from blood to brain in dogs.

The ratio of carbon dioxide (CO2) to bicarbonate (HCO-3) is important in acid-base homeostasis and to the central chemical drive to ventilation. The entry of HCO-3 from blood into the central nervous system (CNS) has been controversial, and the entry of CO2, assumed to be rapid, has not been separated from HCO-3 entry. Therefore the rates of movement of CO2 and of HCO-3 from blood to CNS were evaluated. The first-pass brain uptake of 11C-labeled CO2-HCO-3 was studied under conditions with and without carbonic anhydrase inhibition (CAI), with the isotope injected either as CO2 (acid injectate) or as HCO-3 (alkaline injectate) into the aortic arch of anesthetized dogs. The uptake of 11C under conditions without CAI was about 80% and remained the same whether the isotope was injected as CO2 or as HCO-3. The uptake of 11C under conditions of cerebroventricular administration of acetazolamide was 61.5 +/- 2.0% after injection as CO2 and 56.7 +/- 8.3% after injection as HCO-3. The uptake of 11C under conditions of systemic CAI was 50.3 +/- 3.0% after injection as CO2 and 19.3 +/- 1.1% after injection as HCO-3. The uptakes were comparable for the combination of cerebroventricular and intravenous acetazolamide. From the values for 11C uptake with systemic CAI and the uncatalyzed reaction rates for interconversion of CO2 and HCO-3, the first-pass brain uptake was calculated to be 87.7 +/- 7.8% for CO2 and 16.3 +/- 1.8% for HCO-3. Thus there is a very rapid diffusion of CO2 from blood to brain and a significant movement of HCO-3 from blood to brain.

Acetazolamide↗

Regulation of CSF composition--blocking chloride-bicarbonate exchange.

The possibility that the increase in cerebrospinal fluid (CSF) [HCO-3] observed during respiratory acidosis could be the result of a decrease in CSF [Cl-] was studied by blocking a putative Cl--HCO-3 exchange transport system. Anesthetized dogs (pentobarbital 30 mg, iv) were given either 4,4'-diisothiocyano-2,2'-disulfonate stilbene (DIDS, 0.02 mumol/kg) or pyridoxal 5-phosphate (P-5-P, 4 mumol/kg) in the lateral cerebral ventricles and maintained either normocapnic (RA) or hypercapnic (5% CO2). CSF and arterial Pco2, pH, [Na+], [K+], [Ca2+], [Cl-], and [lactate] were determined. [HCO-3] was calculated. Samples were drawn before and 4 h after the drug was administered. In control dogs on RA no significant change was observed in any measured parameter after 4 h. Dogs receiving either DIDS or P-5-P and on RA had decreased CSF [Na+] of 2-4 meq/l and CSF [Cl-] of 6 meq/l. CSF [HCO-3] in DIDS dogs decreased approximately 5 meq/l. There was no significant change in CSF [HCO-3] in P dogs. After 4 h of 5% CO2, control dogs had decreased CSF [Cl-] of 3 meq/l and CSF [HCO-3] increased approximately 4 meq/l. Dogs receiving DIDS or P-5-P and breathing 5% CO2 for 4 h had decreased CSF [Cl-] of 6-9 meq/l and [HCO-3] increased of 7-9 meq/l. CSF [Na+] did not change during respiratory acidosis in any group. It was concluded the Cl- transport in CSF can be interfered with by use of blocking agents which inhibit Cl--HCO-3 exchange channels.

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

Relationship between central nervous system hydrogen ion regulation and amino acid metabolism in hypercapnia.

Resting level of ventilation is affected by change in hydrogen ion [H+] and by certain amino acid neurotransmitters in the brain and cerebral fluids. Hypercapnia alters both [H+] and amino acid content. Therefore, the effect of 90 min of hypercapnia on blood and cerebrospinal fluid (CSF) contents of selected amino acids and ammonia was studied in anesthetized mongrel dogs using 13N-labeled ammonia. Metabolic turnover of CSF ammonia was not significantly altered by hypercapnia, but CSF equilibrium concentration of metabolized ammonia, i.e., glutamine, a precursor of the neurotransmitters glutamic acid and gamma amino butyric acid, varied linearly with CSF bicarbonate and hydrogen ion concentration. The percentage of CSF glutamine derived from tracer-labeled ammonia metabolized in the central nervous system (CNS) rose from 30% at normocapnia to 60% after 90 min of hypercapnia, whereas at the same time, the CSF transfer rate of glutamine increased by a factor of 2. These observations show that there is a significant correlation between CNS transfer of glutamine and CNS hydrogen ion regulation during hypercapnia.

Acid-Base Equilibrium↗

Prediction of postoperative pulmonary function following thoracic operations. Value of ventilation-perfusion scanning.

Surgical resection of lung cancer is frequently required in patients with severely impaired lung function resulting from chronic obstructive pulmonary disease. Twenty patients with obstructive lung disease and cancer (mean preoperative forced expiratory volume in 1 second [FEV1] = 1.73 L) were studied preoperatively and postoperatively by spirometry and radionuclide perfusion, single-breath ventilation, and washout techniques to test the ability of these methods to predict preoperatively the partial loss of lung function by the resection. Postoperative FEV1 and forced vital capacity (FVC) were accurately predicted by the formula: postoperative FEV1 (or FVC) = preoperative FEV1 X percent function of regions of lung not to be resected (r = 0.88 and 0.95, respectively). Ventilation and perfusion scans are equally effective in prediction. Washout data add to the sophistication of the method by permitting the qualitative evaluation of ventilation during tidal breathing. Criteria for patients requiring the study are suggested.

Adenocarcinoma, Bronchiolo-Alveolar↗

Noninvasive cardiac output determination using inhaled oxygen-15-labeled carbon dioxide.

Inhaled oxygen-15-labeled carbon dioxide (CO2*) is hydrated in the alveolar capillary blood to produce oxygen-15-labeled water (H2O*). This allows noninvasive delivery of a traceable indicator into the pulmonary circulation. Removal of oxygen-15 marker from the lung is a function of pulmonary perfusion. Two techniques were evaluated for computing cardiac output (CO) following single bolus inhalation of CO2*: 1) continuous monitoring of arterial blood activity through an external detector and 2) noninvasive positron imaging of oxygen-15-label washout from the chest and simultaneous emergence of activity in arterial blood. In seven mongrel dogs studied using technique 1, 46 determinations of CO were made from 1.2 to 8.0 l/min and compared with simultaneous indocyanine green dye-dilution determination. Correlation coefficient was 0.90 with slope of linear regression of 1.05. In 12 mongrel dogs studied using technique 2, 23 determinations of CO were made from 0.9 to 9.2 l/min and compared with simultaneous indocyanine green dye determination. Correlation coefficient was 0.985 (P less than 0.001) with slope of linear regression of 0.898. This noninvasive technique (2) for determination of CO is independent of assumptions regarding regional ventilation or perfusion of the lung and appears valid in animal studies.

Animals↗

Modification of phrenic nerve output to hypoxia after two hours of hypercapnia and increased cerebrospinal fluid [HCO3-].

Decreased ventilatory response to hypoxia has been reported in patients with CO2 retention. The CO2 retention increases cerebrospinal fluid (CSF) [HCO3-], which could modify the ventilatory response to hypoxia. In order to evaluate the effect of increased CSF [HCO3-] as a consequence of hypercapnia on the response to hypoxia, phrenic nerve output during 5 min of progressive hypoxia was measured in anesthetized vagotomized and mechanically ventilated dogs when their acid-base was normal and when CSF [HCO3-] had increased. Peak phrenic nerve activity (PPNA), inspiratory time (TI), and expiratory time (TE) were recorded in 2 groups of dogs. Two hypoxic tests were conducted 2.5 h apart in each group. One group had normal acid-base status and the second group after the first hypoxic challenge breathed 10% CO2 for 2 h, and then ventilation was adjusted to bring CSF pH back to normal. The CSF [HCO3-] then had increased by 5.2 mEq/L and CSF PCO2 was 14.6 mmHg higher. With CSF [HCO3-] elevation, PPNA activity in response to hypoxia was significantly depressed, compared with that in animals with normal acid-base balance, TI was increased indicating slowing of nerve discharge, and TE was minimally increased indicating lessening of frequency of neural bursts. We conclude that the metabolic component of acid-base balance in the central nervous system can influence the neural output of the respiratory centers in response to hypoxia as manifested by phrenic nerve output, and increased CSF [HCO3-] seen with hypercapnia is associated with depressed hypoxic response.

Animals↗

T-lymphocyte subsets in smoking and lung cancer: Analysis of monoclonal antibodies and flow cytometry.

In order to determine whether abnormalities of immunoregulatory T-cells occur in patients with lung cancer, we characterized peripheral T-lymphocytes in 26 patients with untreated lung cancer. The results in patients with primary squamous cancer (SC) (n = 10), primary adenocarcinoma (AC) (n = 7), and secondary lung metastases (M) (n = 9) were compared with each other and to subjects without cancer (n = 48), including nonsmokers (n = 29) and smokers (n = 19). We found that OKT3+ (mature, peripheral (T-lymphocytes, including both OkT4+ (inducer/helper) and OKT8+ (cytotoxic/suppressor) lymphocytes, were increased in light-to-moderate smokers, but that OKT4+ cells were decreased n heavy smokers (p less than 0.05). The ratio of OKT4+ to OKT8+ (4/8) lymphocytes, reflecting the balance of immunoregulatory cells, was normal in light-to-moderate smokers, but was decreased in heavy smokers (p less than 0.05). The profile of circulating T-cells in patients with SC was similar to the smokers. In contrast, in patients with AC, we found a decreased percentage of OKT8+ cells (p less than 0.05). The 4/8 ratio was elevated in patients with AC (p less than 0.05). In patients with M, there was a decreased percentage of OKT3+ cells reflected in both OKT4+ and OKT8+ subsets. The 4/8 ratio in patients with M was low. Thus, a number of abnormalities in circulating T-cells was found both in smokers and in patients with lung cancer. These results suggest that immunoregulatory abnormalities contribute to the pathogenesis of lung cancer.

Adenocarcinoma↗

Compensatory hypoventilation in metabolic alkalosis.

Although hyperventilation is a well-known compensatory mechanism in metabolic acidosis, compensatory hypoventilation has been inconsistent and controversial in metabolic alkalosis. Six healthy subjects were studied under baseline conditions and during steady-state metabolic acidosis (seven episodes) and alkalosis (14 episodes). Minute ventilation (VE) fell in metabolic alkalosis and rose in metabolic acidosis. These changes in ventilation were entirely due to reduction and elevation of tidal volume (VT) respectively, while respiratory frequency (f) remained unchanged. Alveolar ventilation fell during metabolic alkalosis and resulted in elevation of arterial PCO2 in all subjects. The ventilatory response to arterial PCO2 in all subjects. The ventilatory response to CO2 breathing was also diminished. There was a linear relationship between PaCO2 and plasma [HCO-3] in metabolic acidosis and alkalosis which was defined as PaCO2 (mm Hg = 0.7 [HCO-a] + 20 (+/- SEM), r = 0.95. Although arterial PO2 and plasma [K+] fell during metabolic alkalosis, minute ventilation did not change upon breathing oxygen and there was no correlation between changes in plasma [K+] and plasma H+ regulation.

Acidosis↗

Regional lung function evaluation with nitrogen-13.

Regional ventilation and perfusion studies are routinely performed with molecular nitrogen-13 (a short-lived positron emitter), a multicrystal positron camera, and a computer. These studies have the advantage of viewing with equal sensitivity all sections of the lung simultaneously. Nitrogen-13 is less soluble than xenon in blood and therefore allows more accurate ventilation imaging. The short half-life of the radiopharmaceutical allows simultaneous ventilation and perfusion scintigraphy of the lung. Unlike other imaging techniques in which the residual radioactivity persists in the lung for hours, nitrogen-13 is rapidly cleared allowing repetitive imaging. Ventilation and perfusion studies are part of the routine preoperative evaluation for lung cancer resection or for bullectomy in patients with chronic obstructive pulmonary disease and for assessment of pulmonary emboli in the presence of chronic obstructive disease.

Adult↗

Pattern of breathing and carbon dioxide retention in chronic obstructive lung disease.

Carbon dioxide (CO2) retention occurs in some but not all patients with obstructive pulmonary disease. In order to assess if the pattern of ventilation modulates CO2 retention, 15 normocapnic (group 1) and 15 hypercapnic (group 2) patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 second (FEV1) less than or equal to 1.0 liter) were studied retrospectively. Utilizing clinical information, anion gap and acid-base nomogram, subjects with superimposed acid-base disturbances were eliminated. Therefore, only patients who exhibited steady state ventilatory patterns were studied. In group 1, mean arterial carbon dioxide tension (PaCO2) was 40 ł 2 torr and mean arterial pH (pHa) was 7.410 ł0.004. In group 2, mean PaCO2 was 52.5 ł1.2 torr and pHa was 7.390 ł0.007. No statistically significant differences between groups were present with respect to age. height, sex, lung volumes and flow rates, diffusing capacity and CO2 production. Minute ventilation was similar in both groups (7.631 liters and 7.81 liters). In group 2, the patients had a significantly higher respiratory rate per minute (22 versus 16.5) and smaller tidal volume (355 versus 463 cc) than the patients in group 1. This pattern of ventilation resulted in a larger dead space ventilation (3.98 liters versus 2.95 liters) and a lower alveolar ventilation (3.82 liters versus 4.61 liters) with consequent CO2 retention. The higher respiratory frequency in the patients in group 2 may be due to vagal stimulation from the lungs since this group had a fivefold greater incidence of chronic bronchitis and a seven-fold greater incidence of cor pulmonale than the patients in group 1.

Carbon Dioxide↗

Electrolyte composition of cerebrospinal fluid in acute acid-base disorders.

Electrolyte composition of cisternal CSF was measured during 4 hours of respiratory and metabolic acid-base disturbance in anesthetized dogs. Three groups of dogs were studied: (1), isocapnic metabolic alkalosis; (2), acute respiratory acidosis; and (3), combined respiratory acidosis and metabolic alkalosis. Cisternal CSF [K+] remained unchanged despite significant changes in plasma [K+], PCO2 and [HCO3-]; suggesting that mechanisms involved in regulation of CSF [K+] continue to operate normally under such conditions. Cisternal [Na+] and osmolality remained unchanged with almost identical reciprocal equimolar changes in CSF concentration of Cl- and HCO3- during the acid-base disorders studied. The regulatory mechanisms involved in this Cl- -HCO3- exchange may be different in different acid-base disorders, but since CSF [Na+] is kept constant, CSF [HCO3-] in any acid-base disorder equals the difference between CSF [Na+] and CSF [Cl-].

Acid-Base Imbalance↗

An index of pulmonary edema measured with emission computed tomography.

Positron camera and short-lived biological isotopes are used to obtain transverse sections of lung volume, blood volume, and total lung water of dog lungs to assess the degree of pulmonary edema in normal and edematous dogs. At equilibration with specific isotope, 30 equally spaced angular profiles of the distribution are collected to obtain transverse section images. Emission computed number is obtained in the lung and heart areas for the images obtained with an intravascular marker (11CO) and intra- and extravascular marker (C15O2). The emission computed number ratio of lung to heart for C15O2 images is an index that is related to degree of edema. Emission computed number related to extravascular water can be obtained from normalized (C15O2--11CO) scintigrams. The technique is noninvasive.

Animals↗

Regional edema formation in isolated perfused dog lungs.

Studies using gravimetric analysis of lungs of frozen animals have suggested that the differences in pulmonary microvascular pressure between non-dependent and dependent lung do not influence the formation of regional pulmonary edema. We wondered if the inability to detect variation in regional extravascular lung water (EVLW) was due to the slow freezing process and, therefore, reassessed the distribution of EVLW in vertically suspended isolated perfused dog lungs with a radioisotopic technique that does not require freezing. Total lung water (TLW), blood or intravascular lung water (IVLW), and EVLW were measured in absolute quantities using a positron camera and the positron-emitting isotopes C15O as a blood label and H2(15)O as a total lung water label. Mean isotopic TLW in 17 lungs that were normal or moderately edematous (wet:dry ratio < 7) was 142 +/- 9 (SE) ml compared to the gravimetric estimate of 148 +/- 7 ml (r = 0.92) and isotopic EVLW was 64 +/- 6 ml compared to the gravimetric estimate of 70 +/- 6 ml (r = 0.8). Analysis of the distribution of regional isotopically measured EVLW in the 17 lungs in various states of spontaneous edema formation revealed a small non-dependent to dependent, gravity-related increase in percent regional EVLW compared to percent regional TLW, which did not vary with the degree of edema in the lung. Serial measurements of absolute regional EVLW in four lungs during spontaneously developing edema also failed to show a disproportionate increase in accumulation of EVLW in any lung zone. Thus, despite the wide variation in microvascular hydrostatic pressure between top and bottom of the vertical isolated lung, edema formation seems to be uniform.

Animals↗