Tarnishing the medical profession's image.
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Biomedical subjects
M Sivarajan
Publications and source records attributed to M Sivarajan.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Temperature correction of arterial blood-gas values.
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Blood Gas Analysis↗
Performance evaluation: continuous lumbar epidural anesthesia skill test.
The evaluation of skills in anesthesiology residents is usually subjective and lacks demonstrable reliability. Therefore, an objective criterion-referenced skill test for measuring performance of continuous lumbar epidural anesthesia was developed. For such a test to be useful, it is necessary to demonstrate agreement among rater-observers. Eight performances of continuous lumbar epidural anesthesia were recorded on video tape and simultaneously rated by nine anesthesiology faculty observers to determine inter-rater reliability. Inter-rater agreement was analyzed by determining coefficient kappa for each item and the entire test. Coefficient kappa for the entire test was 0.82 indicating a high degree of agreement between raters on the performance or nonperformance of various items. Development and utility of skill tests are discussed.
Anesthesia, Epidural↗
Effect of total sympathetic blockade on plasma renin activity during surgery.
The interaction of sympathetic blockade and decreased mean arterial pressure on plasma renin activity during surgery was studied in dogs. Plasma renin activity was measured during lumbar laminectomy before and after sympathetic blockade produced by subarachnoid spinal anaesthesia. Plasma renin activity was significantly increased during laminectomy. Twenty minutes after sympathetic blockade there were marked decreases in mean arterial pressure and plasma renin activity; but with mean arterial pressure continuing to decline, plasma renin activity showed moderate increases at 50 minutes after sympathetic blockade. It is concluded that increases in plasma renin activity seen during surgical operations can be attenuated by sympathetic blockade produced by subarachnoid or epidural spinal anaesthesia, although decreases in mean arterial pressure resulting from the sympathetic blockade continue to provide a stimulus for renin secretion.
Animals↗
Blood pressure, not cardiac output, determines blood loss during induced hypotension.
Cardiac output characteristically decreases during trimethaphan infusion but is well maintained or increased during sodium nitroprusside infusion. We postulated that at similar levels of mean arterial pressure, sodium nitroprusside might be associated with greater blood loss than trimethaphan due to the increase in cardiac output. We studied 20 young healthy patients scheduled for bilateral sagittal osteotomies of the mandible. Ten subjects received trimethaphan and 10 subjects received sodium nitroprusside. Using halothane (0.8% to 1%) and nitrous oxide (60%) for maintenance of anesthesia, trimethaphan or sodium nitroprusside was infused to maintain mean arterial pressure between 55 to 60 torr. Cardiac output was measured in five subjects in each group. Heart rate and cardiac output increased significantly and total peripheral resistance decreased significantly during sodium nitroprusside infusion when compared to trimethaphan infusion. There were no significant differences in duration of hypotension or in blood loss. We conclude that operative blood loss during induced hypotension is determined by mean arterial pressure, not cardiac output.
Adolescent↗
Videotape reliability: a method of evaluation of a clinical performance examination.
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Anesthesia, Spinal↗
An anaphylactoid response to a small dose of d-tubocurarine.
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Adult↗
Effects of glucagon on regional blood flow during cardiogenic shock.
We studied the effects of two dosage levels of glucagon infusion on systemic hemodynamic and regional blood flow measurements during experimental cardiogenic shock in monkeys. Cardiogenic shock was induced in monkeys by embolization of coronary arteries with glass microspheres. Glucagon 1 microgram/kg/min was infused in five monkeys and five remaining monkeys received glucagon infusion at 10 micrograms/kg/min. Radioactive microsphere technique was used to measure regional blood flows. During cardiogenic shock, there were significant decreases in heart rate, mean arterial pressure, cardiac output and rate of rise of left ventricular pressure and significant increases in total peripheral resistance. Blood flows to the heart, brain, kidney and splanchnic bed were markedly reduced. Neither dosage level of glucagon produced any significant improvement in systemic hemodynamic or regional blood flow values. Glucagon produced only nonsignificant increases in splanchnic blood flow during cardiogenic shock. These findings suggest that glucagon infusions in dosages of 1 microgram/kg/min and 10 micrograms/kg/min do not improve systemic or regional hemodynamic status in severe cardiogenic shock.
Animals↗
Polynucleotide recognition by DNA alpha-polymerase.
In a survey of template-primer preference of a mouse myeloma DNA alpha-polymerase, the fastest rate of DNA synthesis was with poly(dT) as template and (rA)24 as primer. Such a preference for poly(dT).oligo(rA) was not observed with other DNA polymerases of mouse origin. DNA synthesis in this system resulted in formation of oligo(dA) chains, not template-length poly(dA); thus, the average enzyme molecule bound to a poly(dT).(rA)24 complex and initiated a new oligo(dA) chain many times during the incubation. Binding experiments revealed that the alpha-polymerase had high affinity for poly(dT). Although the alpha-polymerase did not bind to poly(dl) and failed to replicate it inreactions with a base pair complementary primer, poly(dl) was replicated after a (dT) block had been grafted to its 3'-end and the oligo(rA) primer had been added. In similar experiments, the (dT) block was found to be much more effective than other 3'-terminal blocks in promoting replication of denatured calf thymus DNA. The results indicate that specific base sequences may regulate initiation of DNA syntehsis by this alpha-polymerase.
Cell Line↗
Systemic and regional blood flow during epidural anesthesia with epinephrine in the Rhesus monkey.
Hemodynamic and regional blood flow measurements were made in five rhesus monkeys before and 10, 20, 40 and 80 min after induction of high epidural anesthesia (T1) with lidocaine (1%) containing 1:200,000 epinephrine. Following induction of epidural anesthesia with epinephrine, there were significant decreases in heart rate, mean arterial pressure, cardiac output and myocardial and renal blood flow. The percentage of cardiac output received by the brain was significanly increased following epidural anesthesia with epinephrine, thus evidencing autoregulation to maintain cerebral blood flow. Vascular resistance in the lower extremity was significantly decreased during anesthesia, indicating arteriolar dilatation. Also, during anesthesia, the lungs received a significantly increased proportion of the microspheres, suggesting an increased peripheral arteriovenous shunting of microspheres due to the arteriolar dilatation.
Adjuvants, Anesthesia↗