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D T George

Publications and source records attributed to D T George.

87 records · Page 5Linked to original sources
PubMed1977

Possible relation of prostaglandins to PMN-derived mediators of host metabolic responses to inflammation.

Stimulated rabbit peritoneal polymorphonuclear leukocyte (PMN) preparations simultaneously produce prostaglandin-like material and mediators that induce metabolic alterations in experimental animals characteristic of the host's responses to inflammation. The alterations observed in rats include responses by: proteins, carbohydrates, hormones, trace metals, and total blood neutrophils. This study demonstrates a possible relationship between prostaglandins and PMN-derived substances that mediate plasma zinc depression, hepatic amino acid uptake, and increased numbers of blood neutrophils. Production of these mediators by stimulated-PMN preparations was prevented by 23 muM indomethacin or 93 muM aspirin. Conversely, morphine (2 mM or less) had no detrimental effect on production of these mediators, although, it consistently stimulated production of a substance stimulating total blood neutrophia. In addition, 2 muM prostaglandin E and F stimulated production of substances mediating hepatic amino acid uptake plasma zinc depression, respectively. At this concentration, neither prostaglandin significantly altered production of substances mediating increased numbers of total blood neutrophils. A partial-nitrogen atmosphere, dibutyryl cyclic analogs of AMP and GMP, or homogenization of the PMN had no effect on mediator production. The inhibitory effect of indomethacin and aspirin also was observed with PMN-homogenastes. These experimental observations suggest that prostaglandin synthesis has a function in production of mediators by stimulated-PMN preparations.

Amino Acids↗
PubMed1977

Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses.

Crude mediators from stimulated rabbit peritoneal leukocytes (LEM) engender numerous physiologic alterations in rats, which are similar to those observed during infection. One hour after the intraperitoneal injection of crude LEM, plasma insulin and glucagon concentrations are elevated; at 2 h the hormonal alterations are manifested by a 30% increase in hepatic cyclic adenosine 3',5'-monophosphate (cAMP), glycogen depression, and uptake of 14C-labeled nonmetabolizable amino acid analogues (AA). Plasma hormone concentrations reach maximum levels by 5 h and decline by 24 h. The hepatic concentrations of AA parallel the insulin and glucagon responses and correlate with the inverse of insulin/glucagon molar ratio. In spite of mobilization of hepatic glycogen evident at 5 h, plasma glucose concentrations were transiently depressed. Plasma insulin, glucagon, and hepatic AA concentrations were dose dependent. Plasma insulin and glucagon responses to crude LEM may explain increases in hepatic cAMP, uptake of AA, and glycogenolysis as well as hypoglycemia. These data partially characterize the role of crude LEM, provide an explanation for the stimuli-inducing hyperglucagonemia and hyperinsulinemia during infection. They implicate the endocrine pancreas as a factor regulating the host's metabolic response to infection.

Amino Acids↗
PubMed1976

Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis.

Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.

Animals↗
PubMed1975

Respiratory control in liver mitochondria of rats hosting the walker 256 carcinoma tumor.

The decrease in the respiratory control ratio of mitochondria is a first order process when these organelles are incubated in isotonic sucrose. Furthermore, the initial respiratory control ratios and the rates of loss in respiratory control in liver mitochondria from rats hosting the Walker 256 carcinoma are not significantly different form the same properties of mitochondria from untreated animals.

Animals↗
PubMed1975

The relationship between the bovine heart mitochondrial adenosine triphosphatase, lipophilic compounds, and oligomycin.

The lipid-free particulate preparations of the mitochondrial ATPase require phospholipid for activity and can be inhibited by oligomycin, as has been demonstrated previously. In this communication a steady state analysis of the activation of a particulate preparation of the ATPase by phospholipids and its subsequent inhibition by oligomycin has been carried out. The relative affinity of the ATPase for purified phospholipids has been determined by measuring the Km for activation (Ka) for several phospholipids. The Ka values varied from 30 to 100 mum. The Vmax in the presence of phosphatides varies from 0.29 to 1.11 mumol ATP hydrolyzed/min/mg of protein; no correlation is noted between the relative affinity of the enzyme for a phospholipid and the V max value. Higher V max values are noted with the more acidic phospholipids, however. Sodium dodecyl sulfate and monoolein also activate with Ka values of 25 and 800 mum, respectively. Diglycerides, however, do not activate. With all lipids the ATPase activity stimulated is oligomycin-sensitive. The Ki values for oligomycin range from 0.1 to 0.6 mum. Oligomycin is a competitive inhibitor with respect to all the phospholipids tested except phosphatidylethanolamine and phosphatidyglycerol. It is also competitive with respect to sodium dodecyl sulfate (k-i equals 0.94 mum). In reciprocal plots of activity versus ATP concentration, with and without oligomycin, an intercept consistent with either mixed or partial noncompetitive inhibition kinetics is noted. Comparable K-i values for oligomycin are obtained when calculated assuming either mixed or partial noncompetitive inhibition. The Km for ATP is the same in the unactivated and the lipid activated particulate ATPase; the value obtained is slightly lower than the Km for ATP in the solubilized, purified ATPase. Using a spectrophotometric assay the time required for activation with phospholipid and inhibition with oligomycin has also been determined. This investigation suggests the possibility that activation of the ATPase is due a position to interact with the water-soluble substrate. Consistent with the above suggestion is the supposition that the lipids do not necessarily confer inhibitor sensitivity to the ATPase, but rather allow an oligomycin-sensitive activity to be expressed.

Adenosine Triphosphatases↗
PubMed1975

Control of hepatic glycogen metabolism in the rhesus monkey: effect of glucose, insulin, and glucagon administration.

The effects of intravenous glucose, insulin and glucagon admininistration on the hepatic glycogen synthase and glycogen phosphorylase systems were assessed in the anesthetized rhesus monkey. Results were correlated with measurements of hepatic cyclic AMP (cAMP) concentrations and plasma glucose, insulin, and glucagon concentrations. Both glucose and insulin administration promoted significant inactivation of phosphorylase by 1 min, which was followed by more gradual activation of synthase. Neither glucose nor insulin caused significant changes in hepatic cAMP. Marked hyperglucagonemia resulting from insulin-induced hypoglycemia did not cause increases IN in hepatic cAMP, suggesting that the elevated insulin levels possibly inhibited glucagon action on the hepatic adenylate cyclase-cAMP system. Glucagon administration caused large increases in hepatic cAMP and activation of phosphorylase within 1 min, followed by more gradual inactivation of synthase when it had been previously activated by glucose. Concomitant glucose infusion, with resulting increased plasma insulin concentrations, markedly diminished the duration of hepatic cAMP elevations following glucagon adminstration, again suggesting an insulin inhibition of glucagon action on the hepatic adenylate-cAMP system.

Animals↗
PubMedDate not supplied

Cardiomyoplasty. Latissimus dorsi muscle function and blood flow during isolation.

Cardiomyoplasty is a new surgical treatment for heart failure in which skeletal muscle assists the heart. However, for the first 2 weeks postoperatively, the latissimus dorsi muscle (LDM) remains unstimulated, and during the next 2 weeks, the LDM is stimulated with only one pulse every other heart beat. Thus, for the initial 4 postoperative weeks, minimal systolic assistance is provided. The present study determined if the LDM is capable of providing early assistance. Cardiomyoplasty surgery involves severing the perforating intercostal arteries to the LDM, detaching the LDM from its distal insertion, and wrapping it around the heart. At each of these steps, we measured LDM force development, shortening, and blood flow in six dogs. At control, LDM shortening, work, and power decreased during a 2 min fatigue test: fatigue indices (final/ initial value) for shortening, work, and power were 47.6 +/- 6.9%, 47.5 +/- 7.1%, and 46.9 +/- 6.6%, respectively. Blood flow increased in the proximal (P), mid (M), and distal (D) LDM during the fatigue test. After partial vascular isolation, initial shortening, work, and power decreased by 29.4%, 32.5%, and 31.7% from their respective control values. During the fatigue test, fatigue indices for shortening, work, and power were 24.7 +/- 3.3%, 19.5 +/- 4.6%, and 22.2 +/- 4.7%, respectively, all significantly (p < 0.05) less than control values. Resting blood flows were unaltered. During exercise, flow to the P increased, whereas flow did not increase in M (p < 0.05). Loss of LDM function was most apparent after mobilizing and reattaching the muscle. Initial shortening, work, and power significantly decreased (p < 0.05) by 74.1%, 76.8%, and 74.4%, from their respective control values. During a fatigue test, final values for shortening, work, and power were all near zero. Resting blood flow decreased in the M and D (p < 0.05) and, during exercise, blood flow increased only in P. Thus, LDM function was severely depressed during the isolation procedure. This functional loss is associated with inadequate blood flow responses. Therefore, preconditioning and/or revascularization is needed if the LDM is to provide cardiac assistance shortly after cardiomyoplasty surgery.

Animals↗
PubMedDate not supplied

Selective stimulation of latissimus dorsi muscle for cardiac assist.

The contractile power of the latissimus dorsi muscle (LDM) is used in skeletal muscle cardiac assist (SMCA) to augment the blood pumping ability of a failing heart. The LDM has three anatomically distinct, independently innervate segments-the transverse, oblique, and lateral. There are potential advantages to selectively stimulating these LDM regions. We hypothesized that (1) the three nerve branches could be stimulated selectively to activate individual muscle regions with little or no functional overlap, (2) the three muscle regions would generate similar force, and (3) nerves stimulated in combinations would generate forces corresponding to the sum of forces generated by the individual regions. In acute studies of canine LDM (n=5), regional electromyogram (EMG) and isometric force were recorded while branches of the thoracodorsal nerve were stimulated (via nerve-cuff electrodes) individually and in combinations. Analysis of regional EMG and force confirmed selective activation. Stimulation of lateral, oblique, and transverse branches of thoracodorsal nerve activated 53+/-5%, 20+/-9%, and 36+/-9% of the muscle, respectively; with corresponding developed forces of 48+/-6%, 21+/-8%, and 31+/-8% of total muscle force (R=0.98, p<0.05). Selective activation of LDM is possible with little or no functional overlap; however, the muscle regions were nonuniform. Selective stimulation may ultimately facilitate the use of performance enhancing stimulus protocols for SMCA.

Animals↗
PubMedDate not supplied

Voltage-dependent performance of skeletal muscle pouches: implications for cardiomyoplasty.

Cardiomyoplasty, a new therapy for heart failure, uses autologous skeletal muscle to mechanically assist the heart. The success of dynamic cardiomyoplasty is critically dependent on the contraction strength of the assisting skeletal muscle. Unlike cardiac muscle, skeletal muscle contracts in a graded response to electrical stimulation. However, in current cardiomyoplasty practice, no systematic technique exists to set the stimulating voltage effecting skeletal muscle contraction. The stimulating voltage is simply set to some multiple of the "threshold" voltage. Furthermore, researchers do not consider the role of stimulating voltage when they determine the amount of assistance afforded during cardiomyoplasty. To more accurately assess the value of this heuristic voltage-setting technique, we investigated the role of stimulating voltage on the strength of contraction of the latissimus dorsi muscle. Six New Zealand white rabbits had isovolumic hydraulic pouches constructed from the latissimus dorsi muscle. The muscles were wrapped around a compliant balloon in which isovolumic pressure development was measured during tetany-inducing burst (pulse-train) stimulation. The tetanic plateau of the pouch pressure record was used to measure the effects of stimulating voltage on skeletal muscle contraction. Results indicated that (1) increasing stimulating voltage from two to four times the "threshold" voltage increased normalized pouch pressure from 0.38 +/- 0.21 to 0.78 +/- 0.12 (mean +/- SD) (p < 0.05); (2) the threshold-normalized voltage necessary to cause maximal muscle contraction varied widely (5.7 +/- 2.0, mean +/- SD; range, 3.1 to 9.3); and (3) the current achieving maximal pressure development varied from 5.6 to 31.4 mA (19.9 +/- 10.4 mA).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗