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Biomedical subjects

R Gunther

Publications and source records attributed to R Gunther.

At least 73 records · Page 4Linked to original sources
PubMed1986

The role of ductal obstruction on the course of hemorrhagic pancreatitis in the pig.

The effect of relieving pancreatic duct obstruction after the onset of hemorrhagic pancreatitis was investigated. Hemorrhagic pancreatitis was produced in 20 pigs by a bile salt-trypsin retrograde injection technique. In half the pigs the pancreatic duct was permanently ligated, and in the other half the ductal obstruction was relieved 2 h after the onset of hemorrhagic pancreatitis. The overall mortality rate was the same in both groups by 24 h. No difference was found between the groups in the gross and microscopic appearance of histological samples taken from the pancreas immediately after death. The biochemical parameters measured to assess the severity of pancreatitis such as calcium, BUN, creatinine, glucose, proteins, and hematocrit did not show any difference between the two groups. The serum amylase level, a measure of ductal obstruction, was less at 24 h and even lower at 48 h in the release group as compared to the non-release group. This difference suggests that the ductal obstruction was relieved, as the amylase levels declined at 24 and 48 h. Hemodynamic variables, including cardiac output, pulmonary artery pressure, pulmonary wedge pressure, central venous pressure, and aortic pressure were followed. No significant difference was found in any of these parameters between the two groups. The absence of any significant differences in hemodynamic status, histopathological findings, and biochemical analysis in our pigs, if translatable to man, does not lend support to early operative intervention in gallstone pancreatitis in the hope that those patients who already have hemorrhagic pancreatitis will benefit from early pancreatic ductal decompression.

Animals↗
PubMed1985

Effect of prostaglandin blockers on ascites fluid in pancreatitis.

UNLABELLED: Prostacyclin (PGI2), a potent vasodilator with complex effects on the mesenteric circulation, has been found to be elevated in the hemorrhagic ascitic fluid of pigs with hemorrhagic pancreatitis. This investigation was designed to determine if blockage of PGI2 significantly reduces the volume and/or toxicity of hemorrhagic ascitic fluid associated with hemorrhagic pancreatitis in pigs. Fifteen pigs were studied: five received corticosteroids, five received ibuprofen, and five were untreated. The relative toxicity of the hemorrhagic ascitic fluid was assessed by intraperitoneal injections of the fluid from pigs into mice. RESULTS: (1) hemorrhagic pancreatitis was associated with high levels of PGI2 in blood 15 times and in hemorrhagic ascitic fluid 25 times that of baseline; (2) steroids and ibuprofen blocked PGI2 production (p less than 0.05); (3) neither steroids nor ibuprofen, even when administered as pretreatment, decreased ascites formation; and (4) the mortality rate in mice was significantly reduced (p less than 0.05) in the ibuprofen-treated group as compared with the untreated and steroid-treated groups. CONCLUSION: PGI2 does not play a significant role in the volume of ascites formation. There was an absence of toxicity in the hemorrhagic ascitic fluid of the ibuprofen-treated group.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Pathogenicity of a modified-live pseudorabies vaccine virus in lambs.

Subcutaneous injections of modified-live pseudorabies virus (PRV) vaccine into lambs caused clinical signs and death within 1 week after injection in 4 of 5 inoculated lambs. The clinical signs included depression, high fever, muscle fasciculations and convulsions, occasionally followed by death within 48 hours of the initial clinical signs. Histologic examinations and virus isolation procedures demonstrated PRV in the CNS of infected lambs. Sera from sick lambs remained negative for PRV antibodies. Two subsequent serial passages of the vaccine virus in lambs resulted in similar clinical signs and death in 6 of 10 inoculated lambs. Again, PRV was isolated from tissues of sick lambs, and the histopathologic findings were characteristic of the disease. Affected lambs remained seronegative to PRV, as did lambs that remained clinically normal after inoculation. There was no evidence of PRV transmission to uninoculated lambs and pigs housed with the infected lambs.

Animals↗
PubMed1984

Entry of four cephalosporins into the ovine lung.

Following cannulation of the right external jugular vein and the efferent duct of the right caudal mediastinal lymph node (the caudal end of this node having been ligated to cut off the inflow of systemic lymph), sheep were each given one of four "cephalosporins" (cefazolin, moxalactam, cefoperazone, or ceftriaxone) as single doses injected iv over 30 min. All of the drugs appeared in the pulmonary lymph during iv infusion. Peak concentrations in the lymph were attained at 5 min postinfusion with cefazolin, cefoperazone, and ceftriaxone; the peak for moxalactam was attained at 30 min postinfusion. Cefazolin and cefoperazone penetrated better than did ceftriaxone, which penetrated better than did moxalactam. The concentrations of moxalactam, as compared with the other drugs, declined more gradually in both venous blood and pulmonary lymph. In view of the prompt entry and transit through the lungs and the high concentrations attained in the pulmonary lymph, these drugs should be effective in the treatment of pneumonias caused by susceptible bacteria.

Albumins↗
PubMed1984

Effect of nonprotein colloid on postburn edema formation in soft tissues and lung.

We studied the effect of a nonprotein colloid solution--namely low molecular weight dextran (LMWD)--on edema formation in burned and nonburned soft tissue and lung. Adult sheep with lung and bilateral flank lymph fistulas were given a unilateral 25% to 30% full-thickness burn under ketamine anesthesia and followed for 72 hours. Resuscitation (24-hour period) was performed with lactated Ringer solution (LR) (n = 9) or 10% LMWD in saline (n = 8) to restore baseline vascular pressures and cardiac output. Interstitial edema and microvascular protein permeability were monitored by lymph flow (QL) and lymph to plasma protein ratio, respectively. With LR, QL values in nonburned skin and lung were increased twofold to threefold in the first 24 hours, while with LMWD, values remained at baseline. The nonburn edema with LR was due to the burn-induced hypoproteinemia state. The prevention of this process with LMWD was due to the generation of a twofold to threefold increase in the plasma to interstitial colloid osmotic pressure (COP) gradient. Burn QL was increased fivefold in both groups despite a higher COP gradient with LMWD. Net fluid requirements for the first 24 hours were 75 and 35 ml/kg for animals treated with LR and LMWD, respectively. After cessation of dextran administration in the second 24 hours, the COP gradients for the two groups were equal but QL in nonburned skin and net fluid requirements now increased significantly in the LMWD group. The development of nonburn edema was believed to be due to the persistent hypoproteinemic state. We conclude that edema formation in nonburned tissues, which is due to hypoproteinemia, accounts for a substantial amount of the net fluid requirements after thermal injury. This process can be prevented by infusion of a nonprotein colloid as long as the COP gradient is increased. Edema in burned tissue appears to be unaffected by changes in COP.

Animals↗
PubMed1983

Resuscitation from hemorrhagic shock with hypertonic saline or lactated Ringer's (effect on the pulmonary and systemic microcirculations).

We compared the use of hypertonic salt solution (300 mEq Na/liter) with Ringer's lactate as an initial resuscitation fluid for the treatment of hemorrhagic shock. We monitored vascular pressures and cardiac output as well as microvascular function using chronic lymph fistulae in the lung and soft tissues to reflect transvascular fluid and protein flux. Seven unanesthetized sheep were bled to an aortic pressure of 50 mm Hg (2 hours) on two occasions 4-5 days apart, and were resuscitated initially with either lactated Ringer's (LR) or hypertonic saline (HS) to restore left atrial pressure to baseline. This was followed later by the blood return. We found that cardiac output with HS was significantly increased over that with LR, 8.9 +/- 1.8, compared with 6.0 +/- 1.1, in the immediate postresuscitation period with comparable volumes in both groups. Urine output was increased twofold with HS over LR. The initial pulmonary hypertension seen with LR was eliminated with HS. Lymph flow in lung and soft tissue increased to a comparable degree in both groups, the increase being explained by the degree of plasma hypoproteinemia which was present. We conclude that HS increases cardiac output with less net fluid, decreases pulmonary vascular resistance, and does not result in more edema formation when compared with lactated Ringer's as an initial fluid for treatment of hemorrhagic shock.

Animals↗
PubMed1982

Prostaglandin infusion and endotoxin-induced lung injury.

The use of prostaglandins is currently undergoing clinical trials in respiratory failure accompanying sepsis. The effect of prostaglandin E1 (PGE1) and prostacyclin (PGI2) infusion on endotoxin-induced lung injury, with attention to interstitial fluid flux (QL), pulmonary vascular pressure (Ppa), leukocytes, platelets, and release of the lysosomal enzyme beta-glucuronidase, was investigated. A chronic lung lymph fistula model in sheep was used. Seven sheep alternately received Escherichia coli endotoxin and endotoxin plus PGE at a dosage of 1 microgram/kg/min. Six sheep received PGI2 (0.2 microgram/kg/min) instead of PGE1. Both PGE1 and PGI2 decreased the pulmonary hypertension and the interstitial edema produced by endotoxin primarily through their vasodilatory properties. Prostacyclin seemed to have an additional membrane-stabilizing effect. A rebound increase in QL, Ppa, and platelets occurred when PGE1 or PGI2 infusion was discontinued.

Alprostadil↗
PubMed1982

Involvement of multiple sodium ions in intestinal d-glucose transport.

Brush border membrane vesicles isolated from rabbit small intestine were used to measure the interactions between sodium and glucose transport with a rapid uptake technique. A plot of glucose uptake rate vs. increasing sodium concentration yielded a sigmoid curve. Hill analysis revealed a coefficient of 1.9 +/- 0.02 (+/- SEM), consistent with at least two sodium ions involved in glucose transport. Transport coupling was then measured directly with double-label experiments in which the uptakes of D-glucose and sodium were determined in the presence and absence of cotransported solute. At the earliest time point, the ratio of cosubstrate-dependent sodium transport to glucose transport was 3.2 +2- 0.7 (+/- SEM). We conclude that two or more sodium ions are coupled to glucose transport across the intestinal brush border membranes.

Animals↗
PubMed1982

Pulmonary microvascular response to prostacyclin (PGI2) infusion in unanesthetized sheep.

We studied the effect of prostacyclin (PGI2) infusion and cessation of infusion on the pulmonary microcirculation. We used lung lymph flow (QL) and the lymph to plasma protein ratio as sensitive indices of net fluid (QF) and protein flux (CP). After a 4-h base line period, we infused PGI2 (0.2 micrograms . kg(-1).min(-1) into eight unanesthetized sheep for 2 h. We monitored vascular pressures and lymph during infusion and for another 18 h after PGI2. During infusion, QL and cardiac output increased by 75 and 50%, respectively, over base line, whereas the lymph-to-plasma ratio (L/P) remained constant for both albumin and globulin. This resulted in a significant increase in both fluid and protein flux. Pulmonary vascular pressures remained unchanged, whereas mean aortic pressure decreased. The increase in QF and CP was felt to be due to an increase in the surface area of fluid exchange vessels rather than increased permeability. After infusion, cardiac output rapidly returned to base line, whereas mean QL remained increased by 70% over base line for 2-8 h. Mean L/P decreased from 0.65 to 0.53. Pulmonary arterial pressure and pulmonary vascular resistance increased. The increase in QL and decrease in L/P indicate a rebound increase in pulmonary microvascular pressure in the postperfusion period.

Animals↗
PubMed1982

Acute versus sustained hypoproteinemia and posttraumatic pulmonary edema.

We compared the effect of an acute protein depletion versus a sustained protein depletion on pulmonary edema formation. Acute hypoproteinemia was produced either by a rapid plasmapheresis or as the result of acute hemorrhagic shock and resuscitation. Sustained hypoproteinemia was produced by a 24-hour plasmapheresis or as the result of a 50% body burn. Unanesthetized sheep with lung lymph fistulas were used as the experimental model. In the acute depletion groups an early twofold to threefold increase in lymph flow was seen, reflecting an increase in fluid flux, across the microcirculation, with the increase in lymph flow after resuscitation from shock being identical to that seen in a nonshocked animal with a comparable protein depletion. With restoration of the plasma-lymph oncotic gradient, the lymph flow returned to baseline. The lymph protein content always exceeded 2 gm/dl. In the sustained depletion groups the lymph flow also increased twofold to threefold but remained elevated for over 48 hours despite a rapid restoration of plasma-lymph oncotic gradient. The increase in fluid flux after burn was identical to that after protein depletion alone. In these groups the lymph protein content was below 2 gm/dl, indicating a significant interstitial protein depletion. We conclude that a marked increase in fluid flux is seen after sustained protein depletion that is unrelated to oncotic pressure. This process appears to be related to the degree of washout of interstitial protein, possibly decreasing the viscosity of the interstitial matrix, leading to a more rapid edema formation.

Acute Disease↗
PubMed1982

Effect of diaphragmatic lymphatic contamination on caudal mediastinal node lymph flow in unanesthetized sheep.

Our purpose was to determine the effect of diaphragmatic lymphatics on steady state caudal mediastinal node (CMN) or lung lymph flow in the unanesthetized sheep. After standard lung lymph fistula preparation, in which the CMN efferent was cannulated, nine sheep had an additional extensive cautery procedure in the right chest along the esophagus and diaphragm to sever any systemic lymphatics entering the CMN. This was followed by a similar cautery procedure on the left side, one week later. There was no difference in steady state lymph flow, QL, or in the lymph-to-plasma, L/P protein ratio in any paired study when comparing the bilateral cautery procedure with the right side alone, nor was there any difference in these parameters when this data was compared with that from thirty standard lymph fistula preparations. In addition, diaphragmatic lymphatics were cannulated in five sheep. Mean QL immediately post-surgery was 1.6 +/- 0.4 ml/hr compared to a CMN QL of 6.1 +/- 0.4 ml/hr. By six hours after surgery, diaphragmatic QL decreased to 0.4 +/- 0.2 while CMN flow remained relatively steady. We conclude that residual diaphragmatic lymphatics, if any, entering the caudal mediastinal lymph node, not removed by the standard preparation do not appear to affect steady state CMN lymph flow or L/P ratio, in the normal unanesthetized sheep, especially if measurements are obtained at least 6 hours after surgery.

Animals↗
PubMed1981

Response of the soft tissue microcirculation to prostacyclin infusion.

We studied the effect of prostacyclin infusion on the soft tissue microcirculation. We used lymph flow QL and the lymph/plasma L/P protein ratio to reflect transvascular fluid flux and changes in microvascular hydrostatic pressure, Pmv. Unanesthetized sheep with prefemoral lymph fistulae were infused with PGI2 (0.2 microgram/kg/min) for two hours. Changes in QL and L/P were compared to animals in which Pmv was increased by volume loading. During PGI2, QL was significantly increased, as was cardiac output while mean aortic pressure decreased. The L/P ratio did not decrease to the degree seen with a comparable increase in QL, due to an increase in Pmv. The increase in QL was most likely due to an increase in microvascular surface area. QL remained significantly increased for several hours after infusion and L/P decreased to the same degree as seen with an increase in Pmv. This indicates that Pmv is increased for several hours in soft tissue after infusion, due to a relative increase in venous resistance probably secondary to activation of the renin-angiotensin system.

Animals↗
PubMed1981

Pulmonary injury and prostaglandin production during endotoxemia in conscious sheep.

Prostaglandins F2 alpha, E2, and I2 (as 6-keto-PGF1 alpha) and TxA2 (as TxB2) were measured by radioimmunoassay in plasma and lymph from 12 conscious sheep with chronic lung lymph fistulas given Escherichia coli endotoxin (2-10 micrograms/kg) and followed for 24 h. Endotoxin produced a two-phase pulmonary injury. Phase 1 was characterized by transient severe pulmonary hypertension and increased lymph flow rate (QL). Plasma and lymph PGF2 alpha concentrations increased from base-line values of 0.13 +/- 0.08 and 0.30 +/- 0.10 ng/ml to 0.96 +/- 0.37 and 2.8 +/- 0.80 ng/ml, respectively. Values for TxB2 increased from 0.7 +/- 0.1 to 5.5 +/- 1.1 ng/ml in lymph and to 3.2 +/- 0.6 in plasma. Plasma PGI2 increased from 0.48 +/- 0.29 to 4.97 +/- 1.21 ng/ml and lymph PGI2 from 1.80 +/- 0.73 to 14.19 +/- 2.79 ng/ml. Phase 2 was characterized by moderately elevated pulmonary vascular pressures and a maintained high flow rate of protein-rich lymph. Lung lymph and plasma PGF2 alpha concentrations returned to base line. Lymph PGI2 decreased significantly to 5.23 +/- 2.47 ng/ml, whereas plasma PGI2 decreased to 2.70 +/- 1.07 ng/ml. We conclude that prostaglandins, particularly PGF2 alpha and prostacyclin, are released from the lung after endotoxemia and appear in lung lymph as sensitive indicators of pulmonary microvascular injury. Prostanoid production appears to temporally correspond with changes in the pulmonary microcirculation.

Animals↗
PubMed1981

Pulmonary microvascular injury from lipoxygenase infusion: comparison with endotoxemia.

We compared the response of the pulmonary microcirculation to a 5-hr infusion of soybean lipoxygenase with that seen after endotoxin. We monitored microvascular integrity using lung lymph flow QL and lymph/plasma (L/P) protein ratio in unanesthetized sheep. We noted a twofold to threefold increase in QL and a slight decrease in L/P ratio beginning about 1 hr after onset of the lipoxygenase infusion. Leukocyte count decreased significantly and lymph lysosomal enzyme activity increased. Pulmonary artery pressure initially increased from 16 to 31 mm Hg, then decreased to 25 mm Hg during continued infusion. Platelet count remained constant. Parameters returned to baseline several hours after infusion. This pulmonary vascular pressure and lymph flow response was very similar to that seen in the increased permeability phase of endotoxin. A decrease on the L/P ratio and a constant rather than a decreased platelet count were findings different from those seen after endotoxin.

Animals↗
PubMed1981

The effect of prostacyclin infusion on endotoxin-induced lung injury.

Lung injury produced by endotoxin is characterized by both pulmonary hypertension and increased pulmonary vascular permeability. Prostacyclin (PGI2) has been found to be a vasodilator and a membrane stabilizer. The purpose of this study was to determine the effectiveness of PGI2 in preventing endotoxin injury. Eight sheep with chronic lung lymph fistula were given both Escherichia coli endotoxin (2 microgram/kg) alone and endotoxin plus an immediate infusion of PGI2 (0.1 to 0.2 microgram/kg/min) for a 5-hour period; the studies were performed 4 days apart. The endotoxin injury was characterized by early severe pulmonary hypertension, with pulmonary artery pressure increasing from 18 +/- 0.6 to 40 +/- 3.1 mm Hg and lung lymph flow (QL) increasing threefold. This was followed in about 3 hours by an increase in permeability characterized by an increasing lymph to plasma protein ratio (0.63 to 0.74) and a threefold increase in QL. In seven of eight animals infused with PGI2 the pulmonary hypertension and alteration in QL in the early and later phases were significantly decreased. In four paired studies, prostaglandins PGE, PGF2 alpha, and PGI2 as 6-keto PGF1 alpha were measured in lymph and plasma. PGF2 alpha and PGI2 were significantly increased in lung lymph during the early hypertensive phase immediately after endotoxin injection, but returned to baseline during the later phase. In the PGI2 infusion studies, PGF2 alpha showed the same pattern of response, but PGI2 was increased to much higher levels in lymph and plasma, as compared to values of endotoxin alone. The higher plasma values corresponded with less severe lung injury. The one animal not protected by PGI2 had the lowest plasma PGI2 level. We therefore found PGI2 to protect the lung against injury from endotoxin.

Animals↗
PubMed1981

Leukocytes, platelets, and thromboxane A2 in endotoxin-induced lung injury.

The relationship of leukocytes, platelets, and thromboxane A2 (TxA2) to endotoxin-induced lung injury was studied by use of chronic pulmonary lymph fistula in 12 adult female sheep. Endotoxin-induced lung injury in sheep was characterized by an early pulmonary hypertensive phase followed by a phase of increased capillary permeability. A profound leukopenia occurred early after endotoxin infusion and persisted during both phases of the injury. TxA2 levels (measured as its metabolite thromboxane B2) were significantly increased during the hypertensive phase and then returned rapidly to baseline. Levels were higher in lymph than in plasma, implying local generation in lung. Platelet count decreased transiently later in the permeability phase, rapidly returning toward baseline in animals that survived. The decrease in platelets occurred after TxA2 levels had returned to baseline, suggesting that TxA2 may be coming from sources other than platelets. We conclude that leukocytes appear to play a major role in initiating endotoxin-induced lung injury, and TxA2 may be contributing to pulmonary hypertension. Platelets, on the other hand, seem to be transiently sticking to an already damaged endothelium, with the degree of sequestration indicative of the severity of the injury.

Animals↗