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Biomedical subjects

R H Demling

Publications and source records attributed to R H Demling.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1984

Effect of hemorrhagic shock on endotoxin-induced pulmonary hypertension and increased vascular permeability in unanesthetized sheep.

The lung is very susceptible to sepsis or endotoxin injury in the trauma patient. We studied the effect of an episode of hemorrhagic shock and resuscitation on the prostaglandin-induced pulmonary hypertension and leukocyte-induced increased permeability phase of endotoxin lung injury. Eight unanesthetized sheep with chronic lung lymph fistula were bled 50% of blood volume for 2 hr, then resuscitated. Thromboxane, TxA2, levels increased from 0.1 to 0.6 ng/ml during shock, while blood white cell count decreased. Both parameters returned to baseline while lung lymph flow increased twofold during resuscitation with lymph being protein-poor, indicating no increase in permeability. Lung water was not increased but some pulmonary leukostasis was evident histologically after resuscitation. We then studied the effect of this process on all immediate endotoxin insult. Seven unanesthetized sheep were given 0.7 microgram/kg E. coli endotoxin alone, and again after shock and resuscitation, in paired studies performed 3 days apart. There was no difference in either the early pulmonary hypertension or the later increased permeability phase of endotoxin lung injury when comparing the paired studies, as measured by lymph flow and protein flux. Hemorrhagic shock, despite producing a transient increase in thromboxane and pulmonary leukocyte sequestration, does not accentuate the lung injury of endotoxin if the shock state is adequately resuscitated.

Animals↗
PubMed1984

Effect of endotoxin on the integrity of the peripheral (soft tissue) microcirculation.

Peripheral edema, hypoproteinemia, and increased fluid requirements are characteristically seen with sepsis. Our purpose was to determine whether the soft tissue edema is caused by a direct vascular injury from sepsis or is secondary to hypoproteinemia. We determined the effect of endotoxin on peripheral (soft tissue) microvascular integrity using lymph flow (QL) and lymph/plasma (L/P) protein ratio to reflect fluid flux and increased permeability. Response was compared with that seen in the lung. Fourteen unanesthetized sheep were given intravenous E. coli endotoxin 2 micrograms/kg. Vascular pressures and cardiac output (CO) were maintained constant with the necessary fluid infusion. Lung QL increased two- to fourfold in all animals with lymph being protein-rich, indicating increased permeability. Peripheral QL increased transiently in response to an initial increase in vascular pressure returning rapidly to baseline except in those animals (N = 5) demonstrating hypoproteinemia where QL remained increased by 50 to 75%. The increased QL was totally explained by the degree of protein depletion, with no evidence of increased permeability. To assure an adequate endotoxin exposure to the peripheral microvessels, endotoxin (2 micrograms/kg) was also directly injected into the tissue drained by the soft tissue lymphatic. We noted a characteristic endotoxin pulmonary hypertension phase but, again, no increase in peripheral microvascular permeability was found. We conclude that endotoxemia does not alter peripheral microvascular permeability if tissue perfusion is maintained, while the lung is clearly a target organ. Hypoproteinemia may be responsible for the early edema in soft tissues with sepsis.

Animals↗
PubMed1984

Role of thermal injury-induced hypoproteinemia on fluid flux and protein permeability in burned and nonburned tissue.

We studied the role of hypoproteinemia, induced by a major burn injury, on the edema process in burned and nonburned tissues including the lung in the adult sheep. We used lymph flow (QL) and the lymph-plasma (L/P) protein ratio as indicators of the rate of fluid and protein flux across the microcirculation and into the interstitium. We compared the response after a full-thickness burn to 30% of total body surface plus resuscitation by means of lactated Ringer's solution (n = 8) with a comparable degree of hypoproteinemia produced by plasmapheresis with vascular hydrostatic pressure and cardiac output kept constant. We measured lung QL and soft tissue (prefemoral) QL from both the burned and nonburned areas. A twofold increase in QL and a decrease in the L/P ratio was seen in both lung and nonburned tissue in both burn and plasmapheresis animals, indicating the postburn response to be due to hypoproteinemia with no increase in protein permeability. The QL in burned tissue was increased five to ten times with an increase in the L/P ratio. Four burned sheep were resuscitated with pooled plasma. Restoration of plasma proteins eliminated the increase in QL in lung and nonburned tissue but had no effect on the burn response. In summary, burn-induced hypoproteinemia plays a major role in the edema process in nonburned tissues and is corrected by restoration of plasma proteins. Edema in burned tissue does not appear to be related to this process.

Animals↗
PubMed1983

Effects of anesthesia and surgery on prostanoid concentrations in plasma and pulmonary lymph.

Comparisons were made of plasma and pulmonary lymph concentrations of 6-keto-PGF1 alpha and thromboxane B2 between chronic and acute models of the sheep lung lymph fistula preparation. Pentobarbital anesthetized sheep subjected to acute thoracotomy and artificially ventilated demonstrated significantly elevated pulmonary lymph concentrations of 6-keto-PGF1 alpha and TxB2 for two hours following surgery while venous or arterial plasma prostanoid concentrations increased to a much lesser degree over the same time period. No changes in plasma or lymph prostanoid concentrations were observed in the unanesthetized, chronic lung lymph preparation during a similar baseline observation period. The rates of decrease of pulmonary lymph prostanoid concentrations in the acute model following surgical preparation suggest the requirement of a three hour stabilization period after completion of all surgical procedures before pulmonary arachidonic acid metabolism reaches steady-state conditions.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Improved survival after massive burns.

Sixteen patients with massive burns (exceeding 50% of total body surface) were treated at the University of California--Davis Burn Center in the period of 1980 and 1981. Fifteen had flame burns, and eight had inhalation injuries. Mean burn size was 72% total body surface (range, 51-94) with 20-81% full thickness. Mean age was 27 years. Survival results were compared with a similar group of 13 patients treated in 1978 and 1979, mean age 25, and burn size 65% total body surface. Fifteen of the 16 survived, compared with six of 13 in the early group. Substantial changes in therapy between the time periods resulted in the improvements. These include: 1) early endotracheal intubation with application of PEEP before evidence of pulmonary dysfunction; 2) elimination of Swan-Ganz and central venous lines for early volume resuscitation unless absolutely necessary; 3) the addition of hypertonic saline and protein infusions during the first 24 hours of resuscitation along with Ringer's lactate alone resulting in 30% decrease in fluid requirements; 4) rapid institution of nutritional support beginning by day three using a combination of peripheral hyperalimentation and tube feeding; 5) early eschar excision and grafting beginning in the first week rather than the second or third week as previously practiced. Septic complications and hospital stay were also decreased. Cadaver skin or artificial skin were unavailable. A significant improvement in survival rate was noted after a more aggressive treatment protocol was instituted.

Adolescent↗
PubMed1983

Effects of hypoproteinemia and increased vascular pressure on lung fluid balance in sheep.

We compared the effects of a sustained decrease in plasma oncotic pressure on lung fluid balance with those of an increase in vascular pressure in six unanesthetized sheep. Initial plasma protein concentration of 58.0 +/- 2.2 (SE) mg/ml was quickly reduced to 34.0 +/- 1.4 mg/ml via plasmapheresis and held at this value for 24 h. Red cells were returned with lactated Ringer solution infused at a rate adjusted to maintain central venous pressure; cardiac output and pulmonary vascular pressures also remained at base line. Steady-state lymph flows increased from a base-line value of 8.8 +/- 3.2 to 20.1 +/- 5.6 ml/h, while the lymph-to-plasma protein concentration ratio ( [L/P] ) decreased from 0.65 +/- 0.03 to 0.44 +/- 0.04. Decreased lymph protein resulted in reestablishment of base-line plasma-to-lymph oncotic gradient. The increased lymph flow was not the result of increased filtration forces, since all vascular pressures and the oncotic gradient were unchanged; nor was it due entirely to increased surface area since [L/P] was decreased. The decrease in plasma oncotic pressure, delta pi P, was twice as effective at increasing lymph flow (1.66 ml X h-1 X mmHg-1, delta pi P) as an equivalent increase in microvascular pressure, delta PC, at normal plasma protein concentration (0.82 ml X h-1 X mmHg-1, delta PC). Elevation of microvascular pressure during hypoproteinemia had a greater effect on lymph flow (1.44 ml X h-1 X mmHg-1, delta PC) than at normal plasma protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effect of thermal injury on endotoxin-induced lung injury.

We studied the effects of a burn injury on the response of the lung to endotoxin. Seventeen unanesthetized sheep with lung lymph fistulas were studied. Eight were given Escherichia coli endotoxin (1.5 micrograms/kg) alone and nine were given the same dose 72 hours after a 25% total body surface burn injury. At this time after burn, all physiologic parameters were at baseline levels. A characteristic two-phase lung injury was seen after administration of endotoxin with an initial hypertension phase, characterized by pulmonary artery hypertension, and a second or permeability phase, characterized by an increase in protein-rich lymph flow. all eight animals that underwent only endotoxin administration survived, whereas four of the nine burned animals died during the permeability phase in pulmonary edema. Major physiologic differences between the groups were noted during the permeability phase, including a more severe hypoxia, pulmonary hypertension, and increased postburn lymph flow. Major biochemical changes included significant increases in lymph thromboxane, thromboxane B2, and beta-glucuronidase activity in the burn group. We conclude that the lung is more sensitive to endotoxin after burn, probably as a result of an increased release of products of arachidonic acid metabolism and products of leukocyte activation caused by the body burn.

Animals↗
PubMed1983

The effect of ketamine on endotoxin-induced lung injury.

We investigated the effects of ketamine HCl on endotoxin-induced pulmonary injury in 20 chronically instrumented sheep with lung lymph fistulas. The caudal mediastinal lymph node was cannulated in 20 ewes (45-55 kg). The catheter was externalized and the lymph allowed to drain freely. Pulmonary injury was induced by an intravenous infusion of Escherichia coli endotoxin (1.0-1.5 micrograms/kg body wt) over a 5-min period in 11 animals. The injury was characterized by an increase in pulmonary arterial pressure, pulmonary arterial wedge pressure, and lung lymph flow. There was no change in mean systemic arterial pressure. These changes were significantly attenuated by intravenous administration of ketamine HCl (5 mg/kg) following endotoxin injury in 9 other animals. When ketamine was given, the pulmonary arterial pressure decreased 32%, lung lymph flow decreased 27%, and systemic blood pressure increased 22%. Potential mechanisms for the hemodynamic effects of ketamine HCl in sepsis are discussed with particular reference to the pulmonary microvasculature.

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

Effect of nitroprusside on pulmonary hypertension and lung fluid balance after E. coli endotoxin.

Pulmonary edema after Escherichia coli (E. coli) endotoxin administration is characterized by marked pulmonary hypertension adn microvascular protein permeability. Conceivably, therapy directed at reducing pulmonary arterial hypertension should improve right ventricular mechanics and potentially may decrease the amount of edema formed. We studied the effect of nitroprusside (NP) on pulmonary hypertension, transvascular fluid filtration rate (reflected in lung lymph flow (QL)) and microvascular protein permeability after E. coli endotoxin lung injury. Using the unanesthetized sheep lung lymph preparation, we found the initial pulmonary hypertension after endotoxin infusion refractory to NP. One h after endotoxin, NP significantly reduced the pulmonary artery pressure (P PA) compared to the endotoxin control group. During NP infusion, cardiac output increased a P PA decreased. We found no difference in QL during NP infusion compared to the control group. After cessation of NP infusion, QL increased, whereas protein clearance (QL x lymph protein content) remained constant. We found no beneficial effect of nitroprusside on transvascular fluid flux and microvascular protein permeability after E coli endotoxin injury.

Animals↗
PubMed1982

Mechanisms for redistribution of plasma protein following acute protein depletion.

Acute plasma protein depletion is followed by a rapid and substantial replenishment of the protein deficit. We studied the effects of plasmapheresis on flow and composition of peripheral lymph in 11 unanesthetized sheep. Whole blood was replaced with red blood cells and lactated Ringer solution to reduce plasma protein concentration ([P]) 26-54%. At 24 h after plasmapheresis, [P] had returned halfway to base line. Lymph flow (L) increased immediately after plasma protein reduction, was maximal 3 h later, and remained elevated for more than 3 days. The increase in L was coupled with a decrease more than 3 days. The increase in L was coupled with a decrease in lymph-to-plasma protein concentration ratio ([L/P]). The plasma-to-lymph oncotic gradient was reestablished by 24 h due to the reduction in lymph protein and the partial return of [P]. After 24 h, L remained elevated despite base-line levels for all measured vascular pressures and plasma-to-lymph oncotic gradients. Although lymph flow was increased, the permeability-surface area product for protein was decreased below base line. The data confirm that the partial return of [P] in the first day after plasmapheresis is due largely to a shift of extravascular protein mass into the vascular compartment and show that redistribution is initiated by increased lymphatic return and maintained by a sustained increase in L and a decrease in protein permeability of the plasma-lymph barrier.

Animals↗