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Biomedical subjects

J A Guzman

Publications and source records attributed to J A Guzman.

At least 19 recordsLinked to original sources

Dopamine-1 receptor stimulation attenuates the vasoconstrictive response to gut ischemia.

The effects of fenoldopam, a dopamine-1 (DA-1) receptor agonist, were studied in two groups of anesthetized dogs before and after induction of splanchnic ischemia by way of hemorrhage. During the first portion of the experiment, both groups received fenoldopam (1.5 microg x kg(-1) x min(-1)) for 45 min followed by a 45-min washout. During the second portion, hemorrhage (10 ml/kg) was induced, followed by no intervention in group I (controls) and restarting of the fenoldopam infusion in group II. Prehemorrhage, fenoldopam increased composite portal blood flow by 33% (P < 0.01). After hemorrhage-induced splanchnic ischemia, fenoldopam restored portal vein blood flow to near baseline, maintained the splanchnic fraction of cardiac output, and attenuated the rise in gut mucosal PCO(2). DA-1 receptor stimulation increased portal blood flow and redistributed blood flow away from the serosal layer in favor of the mucosa during basal conditions and after hemorrhage, suggesting a more concentrated distribution of splanchnic DA-1 receptors within the mucosal layer vasculature. Fenoldopam maintained splanchnic blood flow during hypoperfusion and attenuated the splanchnic vasoconstrictive response to hemorrhage.

Animals↗

Gastric anti-ulcer activity of several alpha,beta-unsaturated carbonyl compounds in rats.

The gastric cytoprotective activity of several molecules containing an alpha,beta-unsaturated carbonyl system is reported. We attributed this gastroprotective activity to the presence of a non-hindered Michael acceptor in the molecules assayed and suggested that the mechanism of protection would involve, at least in part, a nucleophilic attack of the sulphydryl group of the gastric mucosa to the beta carbon of the Michael acceptors of the compounds assayed.

4-Butyrolactone↗

Effect of dehydroleucodine in experimental colitis in rats and mice.

Dehydroleucodine (DhL), a sesquiterpene lactone (SQL) of the guaianolide type isolated from Artemisia douglasiana Besser, shows a pharmacological cytoprotective effect and significantly prevents the formation of gastric and duodenal lesions induced by various necrotising agents in rodents. The effects of DhL, on two models of experimental colitis were examined. Colitis was produced in male Wistar rats by rectal instillation of 5 and 10% acetic acid, following the methods of Eliakim et al. and Le Duc et al., respectively. In mice colitis was produced by rectal instillation of 0.1 ml of 2,4,6-trinitrobenzene sulphonic acid (5 mg in 50% ethanol) (TNB) as previously described by Chin et al. In this study, the administration of DhL 40 mg kg(-1)(1 h before the induction of colitis) significantly decreased mucosal damage. This effect was consistent in both models. The protection provided by DhL was accompanied by significant decreases in diarrhoea and colon weight; and histologically normal mucosa without ulceration and mucus production were observed. This study shows that both TNB and acetic acid colitis can be pharmacologically controlled by DhL. Our results suggest that the protective activity of DhL in experimental colitis is mediated, at least in part, through the increase of glycoprotein synthesis, anti-inflammatory effect and inhibition of COX-2 induction, and by inhibiting the degranulation of cells containing monoamines.

Acetic Acid↗

Gut mucosal-arterial Pco2 gradient as an indicator of splanchnic perfusion during systemic hypo- and hypercapnia.

OBJECTIVES: By accounting for influences of systemic acid-base disturbances, gut mucosal-arterial Pco2 gradient (Pico2 - Paco2) has been increasingly advocated as a more specific marker of splanchnic perfusion than Pico2 alone. We examined the stability of the Pico2 - Paco2 gradient compared with raw Pico2 measurements during induced systemic hypo- and hypercapnia. DESIGN: A prospective animal study. SETTINGS: A university research laboratory. SUBJECTS: Twenty anesthetized, paralyzed, and mechanically ventilated mongrel dogs. INTERVENTIONS: After a baseline period during which Paco2 was maintained near 40 torr, the animals were divided into four groups. Minute ventilation was then altered by adjusting tidal volume, frequency, or both to achieve group Paco2 values of 15, 20, 60, and 80 torr for groups 1 through 4, respectively. Portal blood flow was monitored and maintained near baseline levels by infusion of intravenous fluids. Intestinal Pico2 was measured continuously by using capnometric recirculating gas tonometry. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SE) aggregate baseline Pico2 - Paco2 was 16.9+/-3.3 torr. After 60 mins of hypoventilation, Pico2 - Paco2 decreased to 14.2+/-1.1 and to 13.7+/-2.7 torr in groups 3 and 4, respectively (p = NS, compared with baseline for both). On the other hand, after 60 mins of hyperventilation, Pico2 - Paco2 increased to 37.9+/-3.6 and 28.0+/-6.3 torr in groups 1 and 2, respectively (p < .0001, compared with baseline for both). CONCLUSIONS: In this model of maintained portal blood flow, Pico2 - Paco2 remained essentially stable after hypoventilation but increased significantly after inducing hyperventilation. Our findings warrant cautious interpretation of Pico2 - Paco2 as an indicator of splanchnic perfusion during systemic hypocapnia.

Animals↗

Splanchnic hemodynamics and gut mucosal-arterial PCO(2) gradient during systemic hypocapnia.

The effects of hypocapnia [arterial PCO(2) (Pa(CO(2))) 15 Torr] on splanchnic hemodynamics and gut mucosal-arterial P(CO(2)) were studied in seven anesthetized ventilated dogs. Ileal mucosal and serosal blood flow were estimated by using laser Doppler flowmetry, mucosal PCO(2) was measured continuously by using capnometric recirculating gas tonometry, and serosal surface PO(2) was assessed by using a polarographic electrode. Hypocapnia was induced by removal of dead space and was maintained for 45 min, followed by 45 min of eucapnia. Mean Pa(CO(2)) at baseline was 38.1 +/- 1.1 (SE) Torr and decreased to 13.8 +/- 1.3 Torr after removal of dead space. Cardiac output and portal blood flow decreased significantly with hypocapnia. Similarly, mucosal and serosal blood flow decreased by 15 +/- 4 and by 34 +/- 7%, respectively. Also, an increase in the mucosal-arterial PCO(2) gradient of 10.7 Torr and a reduction in serosal PO(2) of 30 Torr were observed with hypocapnia (P < 0.01 for both). Hypocapnia caused ileal mucosal and serosal hypoperfusion, with redistribution of flow favoring the mucosa, accompanied by increased PCO(2) gradient and diminished serosal PO(2).

Alkalosis, Respiratory↗

Gastric cytoprotective activity of dehydroleucodine in rats. Role of nitric oxide.

Previously we reported that dehydroleucodine (DhL), a sesquiterpene lactone, shows gastric and duodenal cytoprotective activity. The mechanism is not mediated by antiacid secretory action; DhL stimulated mucus production and indomethacin pretreatment reduced cytoprotective action. In the present study we demonstrated that the gastric cytoprotective effect is antagonized by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine. The inhibitory action of NG-nitro-L-arginine is reversed by L-arginine, but not D-arginine. The findings suggest that NO is involved in the gastroprotection induced by DhL.

Animals↗

Gastric intramucosal PCO2 as a quantitative indicator of the degree of acute hemorrhage.

PURPOSE: Gastric intramucosal PCO2 (PiCO2) is a marker of splanchnic dysoxia and hypoperfusion that is increasingly used in intensive care medicine. We assessed two methods, saline-balloon tonometry versus continuous capnometric recirculating gas tonometry (CRGT), for detecting changes in PiCO2 in animals subjected to various degrees of hemorrhage and examined whether changes in PiCO2 would correlate with the degree of hemorrhage as assessed by blood loss volume. MATERIALS AND METHODS: Following a baseline equilibration period, 20 anesthetized dogs were subjected to bleeding of 0, 23, 35, 41, or 47 mL/kg. After 30 minutes, the shed blood was reinfused and the experiments continued for an additional 120 minutes. RESULTS: Aggregate baseline PiCO2 was 43 mm Hg by both methods. PiCO2 did not change significantly over time in the control animals by either method. PiCO2 by CRGT rose significantly in each of the other groups at the end of the hemorrhage period and after resuscitation. Similar trends were observed in PiCO2 measured by saline tonometry but were significant only with the most severe hemorrhage. Strong correlation was observed between the degree of hemorrhage and change in PiCO2 by both methods. CONCLUSION: PiCO2 serves as a quantitative indicator of the severity of hypovolemic perfusion failure associated with hemorrhage. Compared with standard saline tonometry, CRGT may be a more sensitive method of monitoring the severity of hemorrhage.

Animals↗

Relationship between systemic oxygen supply dependency and gastric intramucosal PCO2 during progressive hemorrhage.

BACKGROUND: As systemic oxygen delivery (DO2) is reduced, oxygen consumption (VO2) is maintained until a critical level is reached (DO2crit) below which VO2 becomes supply-dependent and anaerobic metabolism ensues. We examined the relationship between gastric intramucosal PCO2 (PiCO2) and the onset of systemic supply dependency. We also compared PiCO2 to mixed venous and portal venous blood PCO2 (PmvCO2 and PpvCO2) to assess their utility as premonitory indicators of supply dependency. METHODS: Six dogs were subjected to stepwise hemorrhage to effect a progressive decrease in DO2. Inflection points for changes in VO2, PiCO2, PmvCO2, and PpvCO2 versus DO2 were determined. RESULTS: Mean DO2crit was 6.0 +/- 0.7 mL x kg(-1) x min(-1), whereas the DO2 at which inflection points occurred for PiCO2 and PpvCO2 were 13.2 +/- 1.4 and 11.2 +/- 1.5 mL x kg(-1) x min(-1), respectively (p < 0.05 for both). CONCLUSION: Continuous monitoring of PiCO2 using capnometric recirculating gas tonometry can serve as an early indicator of systemic hypoperfusion before the onset of systemic supply dependency.

Anaerobic Threshold↗

Gastric cytoprotective activity of dehydroleucodine in rats. Role of prostaglandins.

Previously, we reported that dehydroleucodine (DhL), a sesquiterpene lactone, protected the gastric mucosa of rats from absolute ethanol-induced lesions in a dose-dependent fashion. The mechanism is not mediated by an antiacid secretory action and DhL stimulated mucous production. In the present study, we report the effect of DhL on the mucosal production of prostaglandin E (PGE) and the mucosal release of PGE2 in rats stomach. DhL in acute treatment does not modify these values decreased by previous treatment with indomethacin or absolute ethanol. However, DhL in subchronic treatment significantly enhanced the mucosal production of PGE and the mucosal release of PGE2. Also, indomethacin pretreatment resulted in a significant reduction of the cytoprotective action of DhL. These results indicate the participation of endogenous prostaglandins in DhL protection against ethanol damage. Moreover, we suggest that the gastric protective activity of DhL against ethanol induced gastric mucosal damage is mediated, at least in part, through PGE and PGE2 in subchronic treatment.

Animals↗

Gastric and esophageal intramucosal PCO2 (PiCO2) during endotoxemia: assessment of raw PiCO2 and PCO2 gradients as indicators of hypoperfusion in a canine model of septic shock.

STUDY OBJECTIVES: To validate capnometric recirculating gas tonometry (CRGT) for continuously monitoring gut intramucosal PCO2 (PiCO2) in a septic shock model, and to compare gastric vs esophageal PCO2 vs intramucosal-arterial PCO2 gradients. INTERVENTIONS: CRTG catheters were placed in the stomach and esophagus of six anesthetized dogs. A saline solution filled balloon tonometry (ST) catheter was also placed in the stomach. After equilibration, 3 mg/kg Escherichia coli lipopolysaccharide (LPS) was administered IV. PiCO2 measurements were made at 0, 45, and 90 min post-LPS by ST and continuously by CRGT. RESULTS: Baseline PiCO2 was 41.5+/-1.9 (+/-SE) in the stomach by CRGT, 38.0+/-1.0 by ST, and 43.0+/-4.4 mm Hg in the esophagus (p=not significant). Gastric PiCO2 by CRGT increased to 47.0+/-2.4 mm Hg by 25 min post-LPS (p<0.05), whereas gastric (ST) and esophageal PiCO2 increased significantly by 45 min post-LPS. Good agreement was observed between gastric CRGT and ST measurements (mean bias, 1.3 mm Hg). The PiCO2-PaCO2 gradient increased post-LPS, but was significant only for gastric CRGT measurements 90 min post-LPS infusion. CONCLUSION: CRGT provided continuous gastric PiCO2 measurements that were in close agreement with ST but detected changes earlier than the conventional technique. Continuous esophageal PiCO2 represents a valid alternative for assessing gastric PiCO2.

Animals↗

Continuous assessment of gastric intramucosal PCO2 and pH in hemorrhagic shock using capnometric recirculating gas tonometry.

OBJECTIVES: To test a novel device for continuous monitoring of gut intramucosal PCO2 and pH and to compare its use with conventional intermittent saline balloon-tonometry in a model of hemorrhagic shock. DESIGN: A prospective animal study. SETTINGS: A university research laboratory. SUBJECTS: Eight anesthetized, mechanically ventilated mongrel dogs. INTERVENTIONS: Two balloon-tip tonometry catheters, one conventional and one modified for continuous recirculating gas tonometry, were inserted into each animal's stomach by the oral route. Gastric intramucosal PCO2 was recorded continuously by capnometric recirculating gas tonometry throughout the experiment. After a baseline period of 90 mins, vital signs, arterial and mixed venous blood gases, and intramucosal PCO2 values were obtained by recirculating gas tonometry and by the conventional method. Using a modified Wiggers' model, the animals were then subjected to hemorrhage of up to 45 mL/kg, or the volume required to effect a decrease in mean arterial pressure to < 30 mm Hg. After 30 mins, the shed blood was reinfused and the experiment continued for an additional 30 mins. Vital signs, arterial and mixed venous blood samples, saline tonometry samples, and recirculating gas tonometry readings were obtained immediately before and 30 mins after reinfusion of blood. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD baseline intramucosal PCO2 was 47.6 +/- 9.5 torr (6.3 +/- 1.3 kPa) by capnometric recirculating gas tonometry and 45.8 +/- 3.4 torr (6.1 +/- 0.5 kPa) by conventional saline tonometry (p = NS). By 5 mins after inducing hemorrhage, intramucosal PCO2 by recirculating gas tonometry had increased significantly (49.3 +/- 9.7 torr [6.6 +/- 1.3 kPa]; p < .05), and by 30 mins, it had increased to 59.7 +/- 11.3 torr (8.0 +/- 1.5 kPa; p < .001 compared with baseline). After 30 mins of hemorrhage, the conventional method showed an increase in intramucosal PCO2 to 63.0 +/- 20.9 torr (8.4 kPa +/- 2.8 kPa; p = NS vs. baseline by conventional method; p = NS vs. corresponding recirculating gas tonometry values). Gastric intramucosal pH, as determined by recirculating gas tonometry, decreased significantly at 5 mins after starting hemorrhage (7.13 +/- 0.10 to 7.10 +/- 0.10, p < .02). After 30 mins of hemorrhage, intramucosal pH decreased to 6.88 +/- 0.14 (from 7.10 +/- 0.10) by the conventional saline tonometry technique (p < .01) and to 6.89 +/- 0.10 by recirculating gas tonometry (p < .001 vs. baseline). Intramucosal PCO2 by both techniques remained significantly increased above baseline values 30 mins after reinfusion of the shed blood. CONCLUSIONS: Capnometric recirculating gas tonometry allows continuous and automated assessment of gastrointestinal tract perfusion by providing on-line measurements of intramucosal PCO2, which can also be used to derive intramucosal pH. The technique is able to detect changes in intramucosal PCO2 in response to an induced insult over intervals as short as 5 mins.

Animals↗

End-tidal partial pressure of carbon dioxide as a noninvasive indicator of systemic oxygen supply dependency during hemorrhagic shock and resuscitation.

When oxygen delivery (DO2) critically decreases, oxygen consumption (VO2) becomes supply dependent. We examined whether end-tidal PCO2 (PetCO2) would identify supply dependency during shock. Five dogs (Group I) underwent progressive hemorrhage to decrease DO2 until they could no longer maintain a stable blood pressure. Five additional animals (Group II) were bled until VO2 decreased to 70% of baseline, followed by resuscitation. The PetCO2 versus time inflection point was compared with the DO2 at onset of supply dependency (DO2crit). DO2crit for Groups I and II were 6.9 +/- .4 and 8.1 +/- 1.3, respectively (p = NS), and not statistically different from the DO2 values at which PetCO2 decreased (6.6 +/- .7 and 6.3 +/- .7 mL/kg per min, respectively). AT constant minute volume, PetCO2 effectively indicated the onset of supply dependency and rapidly increased during resuscitation, paralleling the changes in VO2 in this model of hemorrhagic shock.

Animals↗

Development and validation of a technique for continuous monitoring of gastric intramucosal pH.

A novel method for continuously monitoring gastric intramucosal PCO2 and pH was developed and tested. Gas was continuously circulated through a modified balloon-tipped catheter connected to an external closed system fitted with an infrared CO2 sensor to monitor PCO2. Performance of the capnometric recirculating gas tonometry (CRGT) system was tested in vitro using an equilibration chamber and in vivo in six anesthetized dogs. Serial PCO2 measurements were made using CRGT and compared with intermittent PCO2 values obtained by conventional tonometry catheters. In the animal experiments, gastric intramucosal PCO2 and pH were determined before and after inducing hypoxia by decreasing the Flo2 to 0.08. After initial placement, PCO2 determined by the CRGT reached a near plateau within 45 min, and at that time point values were comparable to those obtained by conventional intermittent tonometry. Significant increases in gastric intramucosal PCO2 were detectable by CRGT within 5 min of inducing systemic hypoxia, and there was a concomitant significant decrease in intramucosal pH. Continuous monitoring of gastric intramucosal PCO2 and pH is feasible, has potential advantages over conventional methods, and can provide significant trending information over intervals as short as 5 min.

Animals↗

Mucus synthesis and sulfhydryl groups in cytoprotection mediated by dehydroleucodine, a sesquiterpene lactone.

The aerial parts of Artemisia douglasiana have been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. Dehydroleucodine [1], its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ErOH. It was found in this study that (a) pretreatment of rats with 1 (40 mg/kg, po) caused a significant increase in glycoprotein synthetic activity, approximately sevenfold as large as that of the control; and (b) pretreatment of the rats with the thiol reagent N-methylmaleimide (NEM) significantly diminished the cytoprotection provided by 1. However, the protective effect of 1 was not totally abolished by pretreatment with a combination of indomethacin and NEM, indicating additional mechanisms are involved in the cytoprotective action of 1.

Animals↗

Dehydroleucodine prevents ethanol-induced necrosis in the rat gastric mucosa. A histological study.

The aerial part of Artemisia douglasiana Besser (6) has been used in folk medicine as a cytoprotective agent against the development of peptic ulcer. The dehydroleucodine (DhL), its active principle, significantly prevents the formation of gastric lesions induced by the exposure of the rats to absolute ethanol orally administered. The stomachs of control and experimental rats (after ethanol and pretreated with DhL) were removed, opened along the greater curvature and studied under stereo microscope and with light and scanning electron microscope. Absolute ethanol produced focal visible hemorrhagic lesions, extensive hyperemia, vascular stasis, cell disruption, and necrosis of the mucosa. Abundant mass of mucus was observed with scanning. The stomachs of rats pretreated with DhL showed a reduction of lesions. No hemorrhage and hyperemia were observed. The epithelia of the mucosa had a cobblestone appearance, similar to control rats and was covered by a fine layer of mucus. The mechanism of the protective action of DhL is unknown although it seems to be related to endogenous prostaglandins (PG).

Animals↗

Photoperiod, follicle-stimulating hormone receptors, and testicular function in vizcacha (Lagostomus maximus maximus).

In the present work we investigated the presence of testosterone in serum and follicle-stimulating hormone (FSH) receptors in testes of the vizcacha (Lagostomus maximus maximus), a South American rodent. We also investigated the effect of constant light on both parameters. The control group consisted of vizcachas caught in their natural habitat and maintained under continuous darkness; the experimental group consisted of animals maintained under constant light (1076 lx) for 8 days. The results revealed a significant decrease in serum testosterone and FSH receptors when the animals were maintained under constant light, as compared to the control group. Androstenedione was elevated in the serum obtained from the experimental group. It is postulated that the pineal gland may regulate testosterone secretion through FSH receptors and through an enzymatic blockade in the steroidogenic pathway; this supposition, however, remains to be proved.

Androstenedione↗

Unusual cytoplasmic bodies in chromaffin cells of the adrenal medulla of the viscacha (Lagostomus maximus maximus).

Complex structures can be seen associated with large areas of endoplasmic reticulum of the chromaffin cells in the viscacha adrenal medulla. These structures are cylindrical in shape and are formed by chains of globular subunits. A central lumen is observed within which there are bodies resembling chromaffin granules. Parallel cisternae of the endoplasmic reticulum are arranged surrounding these bodies. The functional significance of these structures in unknown.

Adrenal Medulla↗