Search PubMed⌕ Search

Biomedical subjects

M Sivarajan

Publications and source records attributed to M Sivarajan.

At least 19 recordsLinked to original sources
PubMed2000

Three-dimensional echocardiographic assessment of annular shape changes in the normal and regurgitant mitral valve.

OBJECTIVES: To compare mitral annular shape and motion throughout the cardiac cycle in patients with normal hearts versus those with functional mitral regurgitation (FMR). BACKGROUND: The causes of mitral regurgitation without valvular disease are unclear, but the condition is associated with changes in annular shape and dynamics. Three-dimensional (3D) imaging provides a more comprehensive view of annular structure and allows accurate reconstructions at high spatial and temporal resolution. METHODS: Nine normal subjects and 8 patients with FMR undergoing surgery underwent rotationally scanned transesophageal echocardiography. At every video frame of 1 sinus beat, the mitral annulus was manually traced and reconstructed in 3D by Fourier series. Annular projected area, nonplanarity, eccentricity, perimeter length, and interpeak and intervalley spans were determined at 10 time points in systole and 10 points in diastole. RESULTS: The mitral annulus in patients with FMR had a larger area, perimeter, and interpeak span than in normal subjects (P <.001 for all). At mid-systole in normal annuli, area and perimeter reach a minimum, nonplanarity is greatest, and projected shape is least circular. These cyclic variations were not significant in patients with FMR. Annular area change closely paralleled perimeter change in all patients (mean r = 0.96 +/- 0.07). CONCLUSIONS: FMR is associated with annular dilation and reduced cyclic variation in annular shape and area. Normal mitral valve function may depend on normal annular 3D shape and dimensions as well as annular plasticity. These observations may have implications for design and selection of mitral annular prostheses.

Adult↗
PubMed2000

Three-dimensional reconstructions of normal and aneurysmatic left ventricles in vivo using transesophageal echocardiography.

OBJECTIVE: To perform three-dimensional surface reconstructions to provide spatial delineations of a normal and an aneurysmatic left ventricle, using transesophageal echocardiography. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Eight patients in cardiogenic shock admitted to the intensive care unit and two patients undergoing surgery with general anesthesia. INTERVENTIONS: Using a multiplane transesophageal echocardiography probe, nine echocardiographic cross-sectional images of the heart at approximately 20 degrees angular increments were obtained from midesophageal level in each patient for three-dimensional surface reconstructions. Multiple determinations of cardiac output using the thermodilution principle were also made in each patient to verify the accuracy of three-dimensional data sets. MEASUREMENTS AND MAIN RESULTS: End-diastolic and end-systolic volumes were determined from three-dimensional data sets using the disc-summation method. Stroke volume was derived as the difference between end-diastolic and end-systolic volumes. Stroke volume was also calculated from thermodilution cardiac output measurements and heart rate. Correlation and limits of agreement between stroke volumes derived by the two methods were determined. Three-dimensional wire-frame models of a normal and an aneurysmatic left ventricle at end-systole were constructed from the nine echocardiographic cross-sectional images. Correlation coefficient between stroke volume derived from three-dimensional data sets using the disc-summation method and that measured by the thermodilution method was 0.91 (p < 0.001). Wire-frame models reveal a normal symmetric cavity and an aneurysmal cavity in sharp relief. CONCLUSIONS: Three-dimensional surface reconstruction can be performed from multiple cross-sectional images obtained using an unmodified commercially available multiplane transesophageal echocardiography probe, to reveal the left ventricular cavity in sharp relief. High correlation between stroke volume calculated from three-dimensional data sets and that measured by the thermodilution method attests to the accuracy of the three-dimensional data sets.

Adult↗
PubMed1999

Use of a computerized advanced cardiac life support simulator improves retention of advanced cardiac life support guidelines better than a textbook review.

OBJECTIVE: To determine whether an advanced cardiac life support (ACLS) computer simulation program improves retention of ACLS guidelines more effectively than textbook review. DESIGN: Randomized, controlled trial. SETTING: Academic medical center. PARTICIPANTS: Forty-five anesthesia residents and faculty tested 10 to 11 months after ACLS provider course training. INTERVENTION: Participants were randomized and asked to prepare for a mock resuscitation (Mega Code) with either textbooks or a computerized ACLS simulation program. MAIN OUTCOME MEASURE: Performance on a standardized Mega Code examination that required application of supraventricular tachycardia, ventricular fibrillation, and second-degree Type II atrioventricular block algorithms. Mega Code sessions were administered by an instructor who was blinded as to the subject group. The sessions were videotaped and scored by two evaluators who also were blinded as to the subject group. RESULTS: Participants who used the ACLS simulation program scored significantly higher (mean 34.9 +/- 5.0 [SD] of 47 possible points) than participants who reviewed using a textbook (29.2 +/- 4.9); p < .001. Pass-fail rates for the algorithms were also higher for the group that reviewed with the simulator (mean 2.5 +/- 0.5 of 3 possible passes) than the group that used the textbook (1.6 +/- 1.0); p = .001. CONCLUSIONS: Use of a computerized ACLS simulation program improves retention of ACLS guidelines better than textbook review.

Academic Medical Centers↗
PubMed1998

Halothane, but not isoflurane, impairs the beta-adrenergic responsiveness in rat myocardium.

BACKGROUND: The aim of this study was to identify the mechanisms by which halothane and isoflurane change the myocardial beta-adrenergic signal transduction pathway. METHODS: The authors investigated the influence of volatile anesthetics on the isometric force of contraction of rat papillary muscles. Concentration-response curves for isoproterenol and epinephrine were studied under control conditions and in the presence of halothane or isoflurane. In radioligand receptor-binding studies, the beta-adrenoceptor affinities for isoproterenol and epinephrine were investigated with and without guanosine triphosphate. In addition, the isoproterenol-induced cyclic adenosine monophosphate accumulations in viable cardiomyocytes in the absence and in the presence of halothane were determined by radioimmunoassays. RESULTS: The half-maximal positive inotropic effect of isoproterenol was reached at a half-maximal effective concentration (EC50 value) of 68 nM (33-141 nM; n = 10). A minimum alveolar concentration of 1.3 halothane reduced the positive inotropic potency of isoproterenol (EC50 = 158 nM [118-214 nM; n = 10; P < 0.01 vs. control]), whereas isoflurane did not changed it. This observation held true when the force of contraction was stimulated with epinephrine. Halothane (1.3 minimum alveolar concentration) depressed beta-adrenoceptor high-affinity binding and beta-adrenoceptor agonist affinity in radioligand binding assays, an effect not seen with isoflurane. Halothane shifted the intracellular cyclic adenosine monophosphate response curve of isoproterenol to the right. CONCLUSION: Halothane, but not isoflurane, impairs the beta-adrenergic responsiveness in rat myocardium by reducing the agonist affinity of the beta-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1996

Left ventricular volume calculations using a multiplanar transoesophageal echoprobe; in vitro validation and comparison with biplane angiography.

BACKGROUND: Biplane angiographic and transthoracic echocardiographic volume calculations have shown to be sufficiently reliable in symmetric hearts; however, they are unreliable in the presence of aneurysmatic distortions. Multiplane transoesophageal echocardiography offers unobstructed cross-sectional views of the heart from one stable transducer position with the potential of imaging irregular cavity forms more accurately. It was the purpose of this in vitro study to compare the precision of multiplanar transoesophageal echocardiography to that of biplane angiography in determining left ventricular volumes, especially in aneurysmatic models. METHODS: Seven silicon rubber models of the left ventricle from post-mortem specimens (four with aneurysms) were filled with 30 different volumes (range 153-256 ml, 197 +/- 30 ml). Echocardiographic cross-sections (20 degree rotational steps) were obtained from different transducer positions, utilizing a multiplanar probe with a central rotational axis. Volumes were calculated using the disc-summation method. For comparison the same volumes were determined by standard biplane angiography. The minimum number of echo cross-section necessary to optimize precision was analysed by calculating volumes for each increasing equidistant rotational step. RESULTS: Linear correlation between measured volume using a multiplanar transoesophageal echoprobe and true volume was high (r = 0.97) and significantly better than for biplane angiography (r = 0.88; P < 0.001). Measurement bias and imprecision were also significantly lower with multiplanar echocardiography than with biplane angiography (3.9 +/- 7.1% vs 11.1 +/- 15.4%, and 2.0 +/- 3.7% vs 5.9 +/- 8.3%; P < 0.001). Precision of biplane angiographic volume measurements was significantly influenced by the presence of aneurysmatic distortions. Multiplanar echo volumes, however, were not influenced by left ventricular geometry and transducer positions. Nine echo cross-sections provided optimal precision. CONCLUSIONS: Three-dimensional echocardiographic volume calculations using a multiplanar transoesophageal echoprobe and the disc-summation method provide precise measurements unaffected by left ventricular geometry and transducer position in an in vitro setting. Standard biplane angiography is significantly less precise.

Angiography↗
PubMed1996

Effects of general anesthesia and paralysis on upper airway changes due to head position in humans.

BACKGROUND: In supine patients with their heads in flexion, general anesthesia causes posterior displacement of upper airway structures that is associated with airway obstruction, and extension of the head helps restore patency. However, the independent effects of head position, general anesthesia, and muscle paralysis on upper airway structures are not known. METHODS: Lateral radiographs of the neck were taken in supine patients with the head in flexion and extension, during consciousness, and after induction of general anesthesia and muscle paralysis. The following measurements were made distances from the horizontal plane to the epiglottis, the hyold, and the thyroid cartilage to detect anteroposterior displacements; distances from the transverse plane to the hyold and the thyroid cartilage to detect cephalocaudad displacements; and widths of the oropharynx, the laryngeal vestibule, and the laryngeal sinus. RESULTS: With the head in flexion, anesthesia and paralysis compared with the conscious state caused posterior displacement of the epiglottis, narrowing of the oropharynx, and widening of the laryngeal vestibule. With the head in extension, anesthesia and paralysis compared with the conscious state caused anterior displacements of the epiglottis, the hyold, and the thyroid cartilage, narrowing of the oropharynx, and widening of the laryngeal vestibule and the laryngeal sinus. CONCLUSION: Loss of tonic muscular activity due to anesthesia and paralysis results in anteroposterior displacements of the upper airway structures with flexion and extension of the head that are in the same direction as that of the mandible. Anesthesia and paralysis also widen the dimensions of the larynx. These changes might have implications for instrumentation and protection of the airway during general anesthesia or unconsciousness.

Aged↗
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↗
PubMed1993

Glutathione, cell proliferation, and 1,3-bis-(2-chloroethyl)-1-nitrosourea in K562 leukemia.

We have pursued our findings of glutathione reductase (GSSG-R) deficiency and disturbed glutathione in cancer patients treated with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), by investigating how thiol metabolism, cell proliferation, and the nitrosourea interact in human K562 leukemia. Fasting cells arrested in G greatly increased their reduced glutathione (GSH) in response to growth factors. The rise in thiol began after several hours, peaked before DNA synthesis, and resulted from increased production. BCNU inactivated GSSG-R rapidly, and later retarded, doubled, and greatly prolonged GSH formation before stopping DNA synthesis. Pretreatment unlike post treatment with buthionine-S-R-sulfoximine (BSO) diminished BCNU's ability to block GSSG-R. Enzyme inhibition decreased with falling cellular GSH. In the leukemia system as in vivo, sequential BCNU-induced thiol alterations heralded delayed antiproliferative effects. Drug timing markedly affected both thiol and DNA syntheses. By destroying GSSG-R and delaying the upregulation of thiol synthesis while escalating GSH utilization and requirements, the nitrosourea created a striking and previously unrecognized window of vulnerability for GSH-dependent processes. During this period, altered GSH metabolism could contribute indirectly to BCNU's pleiotropic effects by interfering with DNA alkylation repair, glucose decarboxylation, deoxyribose formation, and possibly by influencing other aspects of proliferation. Acquired GSSG-R deficiency was also an early and sensitive marker for prodrug breakdown and activation.

Buthionine Sulfoximine↗
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↗