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Biomedical subjects

J T Daugirdas

Publications and source records attributed to J T Daugirdas.

At least 73 records · Page 4Linked to original sources
PubMed1988

Acetate causes endothelium-independent increases in cyclic AMP in rat caudal artery.

The mechanism of the vasorelaxant action of acetate is unknown. Because cyclic nucleotides have been linked to vasorelaxation in vascular smooth muscle, we studied the effects of acetate on tissue adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) levels in rat caudal artery. Acetate (4 mM) induced an increase in tissue cAMP levels (control: 5.1 +/- 0.67, acetate: 7.1 +/- 0.97 pmol/mg protein, P less than 0.05), with the increase noted as early as 15-30 s after acetate exposure, and peaking at 60 s. The time course of the cAMP response was compatible with the vasorelaxant effect of acetate against an arginine vasopressin (AVP, 2 X 10(-9) M) contraction. Both the increase in cAMP and the vasorelaxant effect were completely blocked by 10(-3) M 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Acetate increased cAMP levels in 3-isobutyl-1-methylxanthine (IBMX)-treated tissue with an effective concentration producing 50% of the maximum response (EC50) of 1.5 mM, similar to the relaxant EC50 (without IBMX) of 2.2 mM against an AVP contraction. In other experiments, the effect of acetate on cAMP was shown to be independent of endothelium. In contrast, acetate had no effect on tissue cGMP levels, whether the endothelium was present or absent. The results suggest that acetate causes an increase in tissue cAMP levels that is not dependent on presence of a functioning endothelium. The changes in cAMP may be contributory to the vasorelaxant effect of acetate in the caudal artery.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Suppression of neutrophil superoxide production by conventional peritoneal dialysis solution.

The pH of conventional peritoneal dialysis solution is normally in the range of 5.0 to 5.5, because acid has been added during the manufacturing process to prevent caramelization of dextrose during sterilization. We studied the effects of normalizing the pH of conventional peritoneal dialysis solution on superoxide production by normal human neutrophils. At a pH of 6.0, superoxide generation was 4.07 +/- 2.56 (SD) nanomoles per million cells. With normalization of pH to 7.4, superoxide production was 19.3 +/- 7.3 (p less than 0.001). The results suggest that the unphysiologic acidity of conventional peritoneal dialysis solution has deleterious consequences on neutrophil superoxide formation.

Adolescent↗
PubMed1988

First-use reactions during hemodialysis: a definition of subtypes.

We believe that it is worthwhile to separate out two distinct types of first-use reactions: a hypersensitivity type (type A) characterized by anaphylactic signs and symptoms and a non-specific type (type B) characterized primarily by chest pain and back pain. Further research is needed to better define the etiology, the epidemiology, and the pathogenesis of these two subgroups of the first-use syndrome.

Anaphylaxis↗
PubMed1987

Acetate relaxation of isolated vascular smooth muscle.

The vasorelaxant effects of acetate in arginine vasopressin (AVP)-contracted rat tail artery strips were examined in order to study mechanism of action. Dose-dependent relaxation by acetate was found in the clinically important range of 4 to 16 mM. Relaxation was not due to complexing of ionized calcium, persisted after mechanical removal of the endothelium, and was not altered by pretreatment with indomethacin. Although acetate also inhibited contraction by alpha-1 and alpha-2 agonists, the relaxant effect was not altered by destruction of sympathetic nerve terminals using 6-hydroxydopamine. The degree of relaxation in this model by various anions correlated with their lyotropic properties; however, the vasorelaxant effect of acetate exceeded that which would be expected on the basis of its position in the lyotropic series. The vasorelaxant effect of acetate was shared by other short-chain fatty acids that can be conjugated with coenzyme A (CoA), such as propionate and malonate. In contrast, a much lesser or absent relaxant effect was found with nonfatty-acid precursors of acetyl CoA, such as pyruvate, lactate, and alanine. The vasorelaxant effect of acetate was abolished by pretreatment with DIDS, an inhibitor of organic anion uptake, suggesting that cellular uptake of acetate is essential to its vasorelaxant action. The results suggest that the relaxant effect of acetate in vascular smooth muscle is non-specific, is not mediated by prostaglandins, does not depend upon the presence of either endothelium or the sympathetic nervous system, and may be due to metabolism of acetate to acetyl CoA with attendant conversion of ATP to AMP.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Plate, coil, and hollow-fiber cuprammonium cellulose dialyzers: discrepancy between incidence of anaphylactic reactions and degree of complement activation.

During the past 10 years, the incidence of severe anaphylactic reactions during dialysis [type A first-use syndrome (FUS)] at our center has been much lower when using cuprammonium cellulose plate (CC-P) dialyzers (0/37, 750 dialyses) or coil (CC-C) dialyzers (0/32, 500) than when using cuprammonium cellulose hollow-fiber (CC-F) dialyzers (8/21,022 dialyses, p less than 0.005 by Chi-square). To determine if the difference in type A FUS incidence between the three dialyzer types could be explained by differences in complement activation, we compared plasma concentrations of C3a des-arginine (des arg) in patients undergoing dialysis with these three varieties of dialyzers. Plasma C3a des arg values increased markedly in the dialyzer outflow blood with the three dialyzer configurations. The levels were similar with the dialyzer types when results were corrected for membrane surface area. Also, the degree of leukopenia was not markedly different with the three dialyzer types. Our findings suggest that complement activation per unit surface area is similar during dialysis with plate, coil, and hollow-fiber cuprammonium cellulose dialyzers. The lack of correlation between the degree of complement activation and the incidence of type A FUS suggests that membrane-induced complement activation is not of primary importance to type A dialyzer hypersensitivity reactions.

Adult↗
PubMed1987

Induction of peritoneal fluid eosinophilia and/or monocytosis by intraperitoneal air injection.

We hypothesized that intraperitoneal air might be one of the causes of peritoneal fluid eosinophilia. To test our hypothesis, we injected 100-500 ml of sterile air intraperitoneally into 5 patients receiving continuous ambulatory peritoneal dialysis (CAPD). All patients responded with a transient increase in peritoneal fluid nonerythrocyte cell count (peak counts ranging from 23 to 335 cells/mm3, mean peak count 140 +/- 125) lasting 4 days (after injection of 100 ml of air) to 7 weeks (after injection of 500 ml of air). In 2 patients, the cells were predominantly monocytes (80 +/- 6.5%), whereas in 3 patients, eosinophils predominated (63 +/- 12%), while monocytes (30 +/- 19%) also increased. Resolution of peritoneal fluid pleocytosis correlated temporally with absorption of subdiaphragmatic air. Our results suggest that intraperitoneal introduction of air into CAPD patients can induce peritoneal fluid eosinophilia and/or monocytosis.

Ascitic Fluid↗
PubMed1987

Involvement of renal allograft by Fabry's disease.

A man with Fabry's disease received a renal allograft from a heterozygous sister. Renal allograft dysfunction necessitated an allograft biopsy 5.5 years after transplantation. Extensive accumulation of Fabry's disease deposits in the glomeruli, tubules, blood vessels and interstitium was noted.

Adult↗
PubMed1987

Use of lactate as a base in hemodialysis.

The purpose of our study was to investigate the feasibility of using lactate as a complete or partial substitute for acetate in hemodialysis solutions. Six patients, each serving as his own control, were dialyzed once against a dialysis solution containing 40 mM acetate, once against a dialysis solution containing 40 mM DL-lactate and once against a dialysis solution containing 20 mM each of acetate and DL-lactate. Six additional patients underwent hemodialysis using acetate + lactate for a 3-week period, and the blood acid-base values during this period were compared to those obtained during periods when acetate was used. All dialysis treatments were well tolerated without hypotension or other clinical manifestations. When acetate + lactate was used, only a slight delay in the correction of acidosis during dialysis occurred and the net change in the plasma bicarbonate value appeared to be comparable to that measured with acetate. On the other hand, when lactate was used, the increase in the plasma bicarbonate level during and immediately after dialysis was reduced. With acetate + lactate, intradialytic blood D-lactate levels remained between 1 and 2 mM and returned promptly to near baseline within 1 h after dialysis. During 3 weeks of dialysis using acetate + lactate, predialysis plasma bicarbonate values were similar to those achieved when using acetate, but with acetate + lactate, the intradialytic plasma acetate levels were reduced by 50%. The results suggest that DL-lactate merits further evaluation as a potential base for hemodialysis solutions, and that both the D- and the L-lactate isomers are metabolized in maintenance hemodialysis patients.

Acetates↗
PubMed1987

Arteriovenous shunting in experimental liver cirrhosis in rats.

The extent of systemic arteriovenous shunting (arteriovenous anastomotic blood flow) was assessed in rats with experimental liver cirrhosis and control rats by injecting 15 micron microspheres into the left ventricle and measuring the percentage of injected spheres trapped in the pulmonary circulation. Cirrhotic rats with body temperature maintained at 38 degrees C were found to have increased trapping of microspheres in the pulmonary bed when compared with control rats studied under similar conditions (8.2% +/- 2.2% vs. 3.6% +/- 0.8%, P less than 0.05). The extent of arteriovenous shunting was also measured in control rats maintained at various body temperatures (34 degrees to 40 degrees C) with and without prior alpha-adrenergic blockade with phenoxybenzamine (0.1 mg/kg). Both body warming and alpha-adrenergic blockade independently increased the extent of arteriovenous shunting. In cirrhotic rats, body warming also increased shunting. However, in contrast to findings in control rats, alpha-adrenergic blockade did not further increase shunting in cirrhotic rats warmed to 40 degrees C. Moreover, the degree of shunting after combined body warming and alpha-adrenergic blockade was similar in cirrhotic and control rats. Our results indicate that increased peripheral arteriovenous shunting occurs in this model of experimental cirrhosis, and that the increased shunting may be related to altered physiologic regulation of arteriovenous anastomotic blood flow.

Adrenergic alpha-Antagonists↗
PubMed1987

Hemodynamic effects of bPTH(1-34) and its analogue Nle8,18Tyr34bPTH(3-34) amide.

We examined the vascular effects of bovine PTH(1-34) and of an analogue, Nle8,18Tyr34bPTH(3-34) amide, which inhibits adenylate cyclase activation by bPTH(1-34) in a number of in vitro systems. In the conscious dog. bPTH(1-34) injection produced dose-dependent hypotension associated with increased heart rate and cardiac output. The (3-34) analogue had no hypotensive effect in doses up to 6.0 micrograms/kg (1.5 nM/kg). In vitro studies revealed that bPTH(1-34) relaxed pitressin-contracted helical strips from the rat caudal artery. The (3-34) analogue displayed a weak, but definite inhibitory effect against the vasorelaxant effects of bPTH(1-34) with a pA2 of 5.5. The results further characterize the previously established hypotensive and vasorelaxant actions of bPTH(1-34), and suggest that the (3-34) analogue, which inhibits adenylate cyclase generation by bPTH(1-34) in nonvascular tissues, antagonizes the vasorelaxant effects of bPTH(1-34) as well. The results provide suggestive evidence that the vasorelaxant effects of bPTH(1-34) may be mediated by adenylate cyclase.

Animals↗
PubMed1987

Effect of hyponatremia on response to volume depletion in uremic dogs.

It has been suggested that sodium depletion can alter cardiovascular reflexes and vascular sensitivity to pressors. To define the effects of hyponatremia on the hemodynamic response to volume depletion in the setting of uremia, isolated ultrafiltration was performed in acutely uremic dogs previously rendered hyponatremic (127 + 2.5 [SD] mEq/L) for 72 hours by dialyzing against a low-sodium dialysate. Response was compared with that of the same animals in the normonatremic (150 +/- 3.6 mEq/L) condition. Animals in the hyponatremic and normonatremic states had similar initial values of blood volume (hyponatremic 2284 +/- 338 ml, normonatremic 2306 +/- 372 ml, P not significant), mean arterial pressure, cardiac output, and total peripheral resistance, but preultrafiltration body weight in the hyponatremic state was greater (hyponatremic 26.1 +/- 2.4 kg, normonatremic 24.6 +/- 1.7 kg, P less than 0.05). Isolated ultrafiltration was performed until a 30% fall in mean arterial pressure occurred. Body weight at the end of ultrafiltration in the hyponatremic state was still higher (24.7 +/- 2.4 kg) than in the normonatremic state (22.9 +/- 1.5 kg, P less than 0.05). At the end of ultrafiltration, similar values of blood volume (hyponatremic 1871 + 329 ml, normonatremic 1821 +/- 267, P not significant) cardiac output, and total peripheral resistance were again found. The results suggest that, in this model, hyponatremia is associated with an alteration in the relationship between body water and blood volume. The excess body water is difficult to remove by isolated ultrafiltration because blood volume depletion ensues at a higher body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Hemodialysis hemodynamics in an animal model: effect of using an acetate-buffered dialysate.

Acetate-buffered dialysis (procedure A) was performed in conscious, nonuremic, splenectomized dogs. In some animals, dialysis was repeated after sympathectomy with 6-hydroxydopamine. During procedure A, hemodynamic changes were most pronounced 1 minute after starting dialysate flow (acute phase), and included a marked rise in cardiac output, pulse rate, and mean pulmonary artery pressure, but no change in mean arterial pressure (MAP) in intact animals. However, a precipitous fall in MAP was noted in sympathectomized dogs. Plasma acetate levels at this time averaged 2.0 +/- 0.5 mmol/L. Six to 30 minutes into procedure A, hypotension could be demonstrated in the intact, but not in the sympathectomized animals, at which time plasma acetate levels averaged 2.2 to 2.7 mmol/L. At 60 to 90 minutes into dialysis, when plasma acetate levels averaged 3.0 +/- 0.8 mmol/L, hypotension with procedure A was no longer significantly greater than with bicarbonate-buffered dialysis (procedure B). Plasma acetate levels at 30 to 90 minutes correlated with the change in cardiac output (r = 0.86, P less than 0.05) and total peripheral resistance (r = -0.76, P less than 0.05), but not with the decrease in MAP (r = -0.43, P not significant). Substantial hemodynamic changes were not seen when bicarbonate-buffered dialysis was used. Our results suggest that acute hypotension during procedure A in the dog model is prevented by an intact sympathetic nervous system. Hypotension occurring later during procedure A is difficult to demonstrate and does not appear to be accentuated after chemical sympathectomy. During procedure A the increase in cardiac output correlates with plasma acetate level.

Acetates↗
PubMed1986

Transdermal clonidine in mild hypertension. A randomized, double-blind, placebo-controlled trial.

In 30 patients with mild essential hypertension, clonidine hydrochloride was delivered from a skin patch reservoir designed to release medication at a constant rate for seven days. After a four-week washout period, patients were randomized (double-blind) into a clonidine- or a placebo-treated group. Clonidine or placebo was then given for five weeks, followed by a two-week washout period to assess withdrawal from treatment. Blood pressure was controlled in 11 of 15 clonidine-treated patients but in only four of 15 placebo-treated patients. The clonidine-treated group evidenced larger decreases in both systolic and diastolic blood pressures. In the clonidine-treated group, blood pressures and plasma clonidine levels were stable throughout a representative seven-day period. Besides mild skin irritation with both clonidine and placebo patches, few side effects were observed. After discontinuation of clonidine administration, plasma levels declined in a non-log linear manner. There was no rebound hypertension. The results suggest that clonidine delivered transdermally is safe and effective for control of mild essential hypertension.

Administration, Cutaneous↗
PubMed1986

Subxiphoid pericardiostomy for hemodialysis-associated pericardial effusion.

Sixteen patients receiving maintenance hemodialysis in whom moderate-to-large pericardial effusions developed were treated with short-term drainage via a large-bore tube implanted into the pericardial sac. Drainage tubes were implanted using a subxiphoid approach (subxiphoid pericardiostomy) while the patient was under local anesthesia. In seven patients, triamcinolone hexacetonide was instilled into the pericardial sac through the drainage tube at regular intervals. In all patients, a drainage period of two to four days, with or without instillation of nonabsorbable steroids, was associated with resolution of the pericardial effusion. Only one recurrence of effusion was demonstrable over a follow-up period extending from three months to eight years (median, 4.2 years). Complications of subxiphoid pericardiostomy were minor (incisional hernia, wound infection, and small pneumothorax) and easily treatable. Our results suggest that short-term drainage via a surgically implanted drainage tube is an effective and safe treatment of moderate-to-large hemodialysis-associated pericardial effusion.

Drainage↗