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Biomedical subjects

M Sivarajan

Publications and source records attributed to M Sivarajan.

At least 19 recordsLinked to original sources
PubMed1995

Jet ventilation using fiberoptic bronchoscopes.

A fiberoptic bronchoscope is used to facilitate tracheal intubation in cases of difficult direct laryngoscopy. Occasionally, difficulty is encountered in advancing the endotracheal tube after the fiberoptic bronchoscope has been introduced into the trachea. This study tested the feasibility of providing jet ventilation through the suction channel of the fiberoptic bronchoscope as an interim measure under those or similar circumstances. Three commercial models of fiberoptic bronchoscopes with suction channels of 1.2-, 1.5-, and 2-mm diameter, respectively, were tested in a mechanical test lung at varying compliances and resistances using a jet injector connected to an oxygen source at 50 psi. The fiberoptic bronchoscope with the 2-mm suction channel was also studied in seven adult patients who were anesthetized and paralyzed. Jet ventilation was manually performed at the rate of 12/min for 10 min. In the mechanical test lung, the tidal volumes with 1.2-, 1.5-, and 2-mm suction channels were as follows: 280 mL, 490 mL, and 880 mL, respectively, at a compliance of 50 mL/cm H2O and normal resistance; 260 mL, 470 mL, and 820 mL, respectively, at a compliance of 50 mL/cm H2O and high resistance to simulate bronchospasm; 130 mL, 270 mL, and 890 mL, respectively, at a compliance of 20 mL/cm H2O and normal resistance; 120 mL, 220 mL, and 810 mL, respectively, at a compliance of 20 mL/cm H2O and high resistance. In anesthetized, paralyzed patients, oxygen saturation was 96% or more throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of halothane on calcium(2+)-activated tension of the contractile proteins and calcium(2+) uptake and release by the sarcoplasmic reticulum in skinned human myocardial fibers.

Based on studies using skinned myocardial fibers from animals, it has been postulated that one of the major mechanisms by which halothane depresses myocardial contractility is by decreasing the Ca2+ content of the sarcoplasmic reticulum (SR). In this study we examined, in skinned human myocardial fibers, the effects of halothane on Ca(2+)-activated tension development of the contractile proteins and Ca2+ uptake and release by the SR. Left ventricular muscle samples obtained from patients undergoing aortocoronary bypass operations were mechanically skinned and immersed in test solutions equilibrated with N2 and halothane preceded and followed by immersion in control solution (no halothane). To study Ca(2+)-activated tension development of the contractile proteins, free Ca2+ concentrations in the bathing solutions were buffered by EGTA. To study Ca2+ uptake and release by the SR, Ca2+ was loaded into the SR and released with caffeine and the resulting tension transients were measured. Halothane (1%-3%) depressed maximum Ca(2+)-activated tensions (pCa = -log[Ca2+](M) = 3.8) by 5% for each 1% increase in concentration. Tensions generated by submaximum Ca2+ concentrations expressed as a percentage of maximum tension were not significantly decreased by halothane except at 3%. Halothane decreased Ca2+ uptake (IC50 = 1.7%), and increased (by approximately 50%) Ca2+ release by the SR. We conclude that decreased activation of the contractile proteins and Ca2+ uptake by the SR can both contribute to the myocardial depression produced by halothane. Of these, decreased Ca2+ uptake by the SR is probably a major mechanism for halothane depression of myocardium.

Animals↗
PubMed1991

Aerosol propellant interference with clinical mass spectrometers.

Metered dose inhalers containing halogenated propellants may interfere with mass spectrometer quantitation of halogenated inhalation anesthetics. We identify the propellant(s) in a commercially available metered dose inhaler that caused erroneous mass spectrometer readings. In addition, we identify the causes of different types of interference in different mass spectrometers.

Aerosol Propellants↗
PubMed1990

The position and the state of the larynx during general anesthesia and muscle paralysis.

Based on a chance observation in two patients in whom the larynges could be visualized during direct laryngoscopy using topical anesthesia but not after general anesthesia and muscle paralysis, the authors postulated that there will be a shift in the position of the larynx with the onset of general anesthesia and muscle paralysis. To verify this the authors measured the position of larynx in lateral radiographs of necks taken in human volunteers when they were awake, and after induction of general anesthesia and muscle paralysis. The authors found that the hyoid bone and epiglottis were shifted anteriorly and the supraglottic region or the vestibule of the larynx was enlarged with the onset of general anesthesia and muscle paralysis. In addition, the larynx was also stretched longitudinally with wide separation of the vestibular and vocal folds. The authors conclude that consciousness is associated with tonic muscular activity that folds the larynx and partially closes it and that onset of general anesthesia and muscle paralysis opens the larynx wider and shifts it anteriorly, which might make visualization of the larynx during direct laryngoscopy difficult in some patients.

Anesthesia, General↗
PubMed1989

The quotient of mean arterial pressure and heart rate predicts hypoperfusion of collateral-dependent myocardium.

This study tested the hypothesis that the quotient of mean arterial pressure (MAP) and heart rate (HR) (pressure divided by rate = PRQ) effectively predicts myocardial hypoperfusion in regions of myocardium supplied with blood via collateral vessels. Regression analysis of data gathered in a study of the effects of halothane and atrial pacing on the distribution of myocardial blood flow has discovered a strong relationship between the PRQ and the inner-to-outer flow ratio in the collateral-dependent zone (R = 0.78). A significant relationship was also found between PRQ and the ratio of subendocardial blood flow in the ischemic zone to subendocardial flow in the normally perfused zone (R = 0.61). These ratios demonstrate that hypoperfusion of the inner layers of the collateral-dependent zone occurred during the condition of hypotension combined with tachycardia; while normal flow distribution was present if MAP exceeded HR. Halothane (1% end-tidal) did not alter the distribution of coronary flow, indicating that halothane does not cause a coronary steal in this model. The results of this study support the concept that the PRQ is an effective predictor of myocardial hypoperfusion when flow to ischemic zones is delivered by collateral vessels in nonfailing, canine hearts.

Animals↗
PubMed1987

Biotransformation of primaquine in vitro with human K562 and bone marrow cells.

Although the antimalarial activity, hemolytic and methemoglobinemic side effects, and detoxification of primaquine are all thought to depend on various biotransformation products of the drug, their site and mechanism of formation and degradation are unknown and their specific biologic effects remain very poorly understood, particularly in humans. We have therefore explored the feasibility of studying primaquine metabolism in cultured human cells. We found that the biotransformation of primaquine can be investigated in vitro in serum-supplemented liquid cultures of partially synchronized and exponentially growing human erythroleukemic K562 cells. Further, these cells can be replaced by cells present in normal bone marrow. Primaquine is rapidly and predominantly converted in vitro into carboxyprimaquine (CPQ) in a quantitative manner and without further modification. In addition to CPQ, a compound Xc that is not 6-methoxy-8-aminoquinoline, and is not derived from CPQ, appears in minor amounts in a delayed fashion. With the K562 as well as with the bone marrow cells the formation of CPQ from primaquine can be totally blocked by large concentrations of the nitrosourea, 1,3-bis-(2-chloroethyl)-nitrosourea (BCNU). With bone marrow, increasing blockade of CPQ formation by BCNU leads invariably to a progressive and striking accumulation of Xc. The availability of reproducible, quantitative, and practical new tools for the study of primaquine metabolism in vitro raises a number of challenging questions and may improve understanding of the mode of action, toxicology, and pharmacogenetics of 8-aminoquinolines.

Biotransformation↗
PubMed1986

Measurement of the incorporation of orally administered arachidonic acid into tissue lipids.

The applicability of a stable isotope method to monitor the mixing of dietary arachidonic acid with endogenous arachidonic acid in tissue lipids was evaluated. Rats were fed octadeuterated arachidonic acid during a 20-day period, and the entry of the dietary acid into lipid esters of various tissues was examined by gas chromatography-mass spectrometric (GC-MS) analysis of their fatty acids. The rats were maintained on a fat-free diet from weaning until 63 days old to enhance the ratio of the dietary acid to endogenous arachidonate. Three separate forms of eicosatetraenoic acid in the tissue lipids could be distinguished by GC-MS: octadeuterated arachidonic acid (recent dietary origin), unlabeled arachidonic acid (maternal origin) and unlabeled 4,7,10,13-eicosatetraenoic acid (originating from palmitoleic acid). The total eicosatetraenoic acid in the tissue lipids contained about 90% arachidonate from recent dietary origin in lung, kidney, heart and fat, 70% in muscle and liver and 27% in brain. The n-7 isomer of eicosatetraenoic acid was estimated to make up 6% or less of the total eicosatetraenoic acid in lung, kidney, brain, muscle and heart tissue lipids, but it comprised around 15% of the total eicosatetraenoic acid in liver. The unlabeled arachidonic acid of maternal origin thus comprised only about 10% of the eicosatetraenoic acid in all tissues examined except muscle and brain, where it was 24% and 70% of the eicosatetraenoic acid, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Metabolic products of arachidonic acid in rats.

The pattern of eicosanoid metabolites appearing in urine and feces following oral administration of radioactive arachidonic acid was investigated using rats deficient in essential fatty acids. About 70-80% of the radioactivity in the urine during the first day after feeding was adsorbed to XAD-2 resin and represented eicosanoid metabolites, whereas the rest of the radioactivity was mainly 3H2O. The eicosanoid metabolites were fractionated into different polarity classes using reverse phase Sep-Pak C18 cartridges. Gas chromatographic analysis of the urinary metabolites following their derivatization into methyl ester-methoxime-tert-butyl-dimethylsilyl ethers revealed that nearly one-half of the metabolites had ECL values less than 22 and represented metabolites more oxidized than commonly described. Only 30% of the metabolites had ECL values between 26 to 32, corresponding to the values for the metabolites that originate from exogenously infused prostaglandins. A large portion of the eicosanoid metabolites was also excreted with the feces. The isotopic patterns from the reverse phase chromatography indicated that many of the fecal metabolites may be similar to those in urine although some metabolites in feces were not present in urine. Based on the specific radioactivity of the administered arachidonic acid, it appeared that at least 6 to 8 mg of eicosanoid metabolites were excreted through urine and feces within 24 hrs following an oral bolus of 60 mg arachidonic acid. The rapid increase and subsequent decrease in eicosanoid metabolite excretion after oral administration of arachidonate indicates that the dietary intake of polyunsaturated fatty acids may have a more rapid effect upon the endogenous production of eicosanoids than is generally recognized.

Administration, Oral↗
PubMed1985

Effect of halothane on coronary collateral circulation.

The authors studied the effect of halothane in a canine model of coronary collateral circulation secondary to chronic occlusion of a coronary artery. Two sets of experiments were performed. In the first experiments, Ameroid constrictors were placed around the left anterior descending coronary artery to produce complete occlusion in three weeks. An inflatable occluder was placed around the circumflex coronary artery in order to apply a mild stenosis to the artery supplying the collateral vessels to produce vasodilation distal to the stenosis. Regional myocardial blood flows were measured using radioactive microspheres. Blood flows to normal and collateralized myocardium were decreased significantly during halothane anesthesia, but perfusion of the subendocardium in both regions was maintained even in the presence of mild stenosis of the circumflex coronary artery supplying the collateral vessels, as indicated by unchanged endocardial/epicardial blood flow ratios. In the second experiments, chronic occlusions of both circumflex and right coronary arteries were produced using Ameroid constrictors. In these animals, sedated using xylazine, pacing-induced tachycardia produced a marked but reversible decrease in blood flow to the collateralized subendocardium. During halothane anesthesia at normal heart rate, blood flow to the collateralized subendocardium was well maintained, but tachycardia produced marked decrease in blood flow to the collateralized subendocardium, leading to the demise of four of seven dogs. The authors conclude that in this chronic canine model, in which control measurements were made during sedation using xylazine, coronary collateral blood flow is well maintained during halothane anesthesia at normal heart rate, but tachycardia during halothane anesthesia severely limits blood flow to the collateralized subendocardium.

Animals↗
PubMed1985

Regional blood flows during induced hypotension produced by nitroprusside or trimethaphan in the rhesus monkey.

In monkeys anesthetized with 70% nitrous oxide and 0.5% inspired halothane in oxygen, we measured changes in systemic hemodynamics and regional blood flows produced by nitroprusside and trimethaphan. Regional blood flow measurements were made using the radioactive microsphere technique. Control measurements were made before infusion of nitroprusside and trimethaphan into each animal in sequence in amounts adequate to reduce mean arterial pressure to approximately 55 +/- 5 mm Hg. Measurements were made during each drug infusion after a stable period of hypotension lasting at least 30 min. During nitroprusside infusion, cerebral blood flow remained unchanged, but myocardial blood flow increased significantly. However, pressure-rate product, an indirect measure of myocardial oxygen consumption, was unchanged, implying that myocardial blood flow exceeded myocardial oxygen requirement. During trimethaphan infusion, cerebral blood flow decreased, although cerebral metabolic rate for oxygen was unchanged due to increased oxygen extraction by the brain. Trimethaphan also produced a decrease in myocardial blood flow that was in proportion to the decrease in myocardial oxygen requirement as indicated by pressure-rate product. Neither drug produced changes in renal or total hepatic blood flows. We conclude that brain oxygen reserve is decreased during hypotension induced by trimethaphan. Blood flows to other organs are not significantly impaired in monkeys during hypotension to a mean arterial pressure of approximately 55 mm Hg induced by either nitroprusside or trimethaphan.

Animals↗
PubMed1984

Regulation of intracellular arachidonate in normal and stressed endothelial cells.

The uptake of arachidonate and stearate from serum-free media by endothelial cells was investigated over a 48 h period. Arachidonate was rapidly incorporated into both the phospholipids and triacylglycerols. Triacylglycerol incorporation reached a maximum at 2 h and then rapidly declined with a concomitant increase in phospholipid incorporation. High initial arachidonate incorporation into phosphatidylcholine was followed by a partial transfer of that arachidonate to phosphatidylethanolamine. In contrast, stearate was slowly incorporated into all of the phospholipids and was not incorporated into the triacylglycerols. Cells stimulated with A23187 for 24 h cleaved stearate from all the phospholipids equally, whereas more arachidonate was cleaved from phosphatidylethanolamine than from the other phospholipids. Released arachidonate was both metabolized and reacylated into the triacylglycerols. Our results suggest that triacylglycerols serve as a modulator of intracellular arachidonate concentrations in endothelial cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Iron supply for erythropoiesis in the rabbit.

Marrow radioiron uptake and marrow blood flow were measured in order to evaluate iron supply for erythropoiesis. Normal, phenylhydrazine-treated and bled animals were studied. The plasma iron turnover of seven normal rabbits was 1.49 +/- 0.22 mg/dl whole blood per d, of 11 rabbits treated 4 d before with phenylhydrazine was 5.16 +/- 1.81, and of four bled animals the plasma iron turnover was 3.75 +/- 1.61. The cardiac output and the percentage of blood flow to the marrow was increased in phenylhydrazine-treated and bled animals. Marrow iron flow in phenylhydrazine-treated animals was 38.3 +/- 32.6 micrograms/min per kg as compared with control values of 7.0 +/- 1.3 (P less than 0.01). This was due to an increase in marrow flow, an increase in plasma iron, and an increase in plasmatocrit. In bled animals, in spite of an increased marrow blood flow, marrow iron flow of 7.3 +/- 2.2 was similar to that of control animals due to a lower plasma iron concentration. The calculated marrow iron extraction of 3.7 +/- 2.4% in phenylhydrazine-treated animals was not different from that of control animals of 4.3 +/- 1.1, whereas extraction was increased in bled animals to 7.9 +/- 1.3 (P less than 0.01). In additional studies of transfused animals, acutely induced anemia was associated with an increased cardiac output, but also with a relative decrease in marrow flow, which left marrow iron supply unaffected. It would appear from these studies that an important mechanism for meeting the increased iron requirement of the hyperplastic erythroid marrow is an increase in marrow blood flow.

Animals↗
PubMed1984

Regional blood flow in dogs during halothane anesthesia and controlled hypotension produced by nitroprusside or nitroglycerin.

We used the radioactive microsphere method to measure and compare the effects of sodium nitroprusside (SNP) and nitroglycerin (NTG) on organ blood flow during hypotension induced by each drug. The study was done in 10 dogs anesthetized using 0.7% end-tidal halothane. Each animal received both SNP and NTG to decrease the mean arterial blood pressure (MABP) to 45 mm Hg, but the sequence in which the drugs were administered was alternated. Five of the dogs received SNP first and five received NTG first. Organ blood flow was measured after a stable period of hypotension that was brief by necessity in order to avoid cyanide toxicity due to increasing dose requirements for SNP. Measurements were made before and during hypotension induced with each drug. The mean duration of stable hypotension was shorter (P less than 0.05) with NTG (5 +/- 1 min) (mean +/- SEM) than with SNP (7 +/- 1 min). During NTG-induced hypotension, blood flows to the brain, kidneys, liver, gastrointestinal tract, pancreas, and skeletal muscle were maintained at control levels. During SNP-induced hypotension, blood flows to the myocardium, liver, gastrointestinal tract, pancreas, and skeletal muscle were maintained at control levels. NTG increased myocardial blood flow (P less than 0.05), while SNP decreased blood flow to brain (P less than 0.05) and kidneys (P less than 0.01). Both drugs decreased blood flow to the spleen (P less than 0.001). Our results indicate that during the first few minutes of NTG-induced hypotension, blood flows to all organs except the spleen are well-maintained, while the first few minutes of SNP-induced hypotension are associated with decreases in blood flow to brain and kidneys as well as to the spleen.

Animals↗
PubMed1984

Objective evaluation of clinical performance and correlation with knowledge.

In certifying competence of anesthesiologists who have finished residency training, knowledge and judgment are evaluated objectively using written and oral examinations. Clinical motor skills, however, are not routinely assessed by objective techniques. This implicitly assumes that knowledge and judgment correlate with performance of motor skills. This study was designed to evaluate whether performance of a particular motor skill correlates with performance on a knowledge test related to that skill. To do this, we developed a criterion-referenced Spinal Anesthesia Skill Test and a knowledge test using multiple-choice questions related to spinal anesthesia. Both the skill and knowledge tests were administered to 44 residents at various levels of training at five major anesthesia teaching programs. Scores on the skill test were significantly higher than in the knowledge test, suggesting that proficiency in this essential motor skill is achieved earlier in training. There was no correlation between scores on the skill test and knowledge test. There were institution-linked differences in the scores on the skill test, suggesting that teaching of motor skills is not uniform. The advantages of developing criteria of performance of motor skills is discussed.

Anesthesia, Spinal↗
PubMed1983

Regional blood flow during cardiopulmonary resuscitation in dogs using simultaneous and nonsimultaneous compression and ventilation.

We studied regional blood flow (QR) using radiolabeled microspheres and measured hemodynamic variables in 20 anesthetized dogs in normal sinus rhythm and during ventricular fibrillation treated with cardiopulmonary resuscitation (CPR). Nonsimultaneous compression and ventilation CPR (NSCV-CPR) was performed in seven dogs with a pneumatic piston that gave 50 chest compressions/min with an open airway with 10 ventilations at an airway pressure of 33 mm Hg interposed between each fifth and sixth compression. Simultaneous compression and ventilation (SCV-CPR) was performed in seven dogs with the piston and in six other dogs with a circumferential pneumatic vest. Both devices gave 30 compressions/min simultaneously with 30 ventilations that elevated airway pressure to 80 mm Hg., The abdomen was bound during SCV-CPR. Regional blood flow (mean +/- SD) to the cerebral hemispheres, cardiac ventricles, and kidneys, expressed as ml/min/100 g tissue, was 3.1 +/- 4.0, 3.4 +/- 3.3 and 1.5 +/- 1.5, respectively, during NSCV-CPR; 11.5 +/- 5.9, 4.9 +/- 4.7 and 2.7 +/- 2.7 during SCV-CPR (vest); and 16.2 +/- 7.2, 11.0 +/- 4.0 and 20.1 +/- 20.2 during SCV-CPR (piston) (all p less than 0.05 compared with NSCV-CPR). These results indicate that QR to all organs studied is reduced below normal sinus rhythm levels during CPR for ventricular fibrillation, QR to the brain is proportionately greater than QR to the heart and kidneys, and QR to the brain is greater with both forms of SCV-CPR than with NSCV-CPR.

Animals↗