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Biomedical subjects

R H Demling

Publications and source records attributed to R H Demling.

At least 127 records · Page 7Linked to original sources
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

Effect of dextran-70 on increased microvascular fluid and protein flux after thermal injury.

The effect of a colloid (dextran-70) infusion on increased microvascular fluid and protein flux after thermal injury was compared with that seen with a crystalloid infusion. Lymph flow (QL) and lymph/phasma (L/P) protein content were used to monitor microvascular fluid flux and protein permeability in the lung and in burned and nonburned soft tissues, namely, skin and subcutaneous tissue, for 72 h in 13 sheep given a 30% TBS full-thickness burn. Vascular pressures were maintained constant with dextran in saline or lactated Ringer's. Mean fluid requirements for dextran were one-half that for crystalloid during the 24-h resuscitation period. However, plasma proteins decreased by 50% with dextran compared to 30% with crystalloid. An increase of 2-2.5 fold in QL was seen during resuscitation in the lung and nonburned soft tissue with crystalloid while the L/P protein ratio decreased, indicating no change in protein permeability. This QL response was prevented during dextran infusion. A rebound increase in soft tissue QL occurred after discontinuation of dextran, probably as a result of the severe residual hypoproteinemia. Burn QL and L/P were markedly increased during the entire 72-h period, indicating increased permeability. Dextran infusion accentuated the QL response in the burn microcirculation. We conclude that dextran decreases edema in nonburned tissue, but appears to increase the protein loss from burn tissue.

Animals↗
PubMed1982

Animal research on hypovolemic shock and resuscitation: an update.

Animal studies have indicated that volume resuscitation is successful with salt-containing crystalloid solutions as well as colloid solutions. Hyperosmolar salt solutions appear to have benefits over isosmolar solutions. Both, however, produce hypoproteinemia, which can lead to edema formation due to changes in the transcapillary oncotic gradient and possibly by changing the interstitial matrix. The lung appears to be much more resistant to edema formation than the soft tissues. Except for the dog, the lung does not appear to be significantly altered from shock with no substantial increase in protein permeability being evident in most studies. Colloid therapy, either proteins or dextran, effectively restores cardiovascular stability after hypovolemia and also prevents the increased transcapillary fluid flux seen in the lung and soft tissues, the former not appearing to be of much clinical significance, while the latter may lead to significant tissue edema. Blood replacement is necessary to restore adequate oxygen delivery to the tissues. The ideal hematocrit appears to be around 30-35.

Adrenal Cortex Hormones↗
PubMed1982

Inhibition of endogenous thromboxane synthesis by exogenous prostacyclin during endotoxemia in conscious sheep.

The relationship between prostacyclin and thromboxane activity in plasma or lymph of endotoxemia sheep was studied to better understand the physiologic significance of these two vasoactive compounds. Conscious sheep received either endotoxin alone or endotoxin plus a five-hour infusion of prostacyclin. Endotoxin alone produced a pulmonary arterial hypertension, a significant decrease in cardiac output, an increase in the lung lymph flow rate, and a leukopenia. Plasma prostacyclin and thromboxane concentrations were elevated to the same extent, while pulmonary lymph thromboxane concentrations were greater than those of prostacyclin. The administration of exogenous prostacyclin significantly attenuated the hemodynamic changes following endotoxin, but not the leukopenia. During the prostacyclin infusion, plasma and lymph prostacyclin concentration were tenfold higher than those seen with endotoxin alone, while thromboxane concentrations were six to eightfold lower. Thus, high circulating prostacyclin concentrations resulted in an inhibition of thromboxane production with an associated attenuation of the hemodynamic response to endotoxin.

6-Ketoprostaglandin F1 alpha↗
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

Effect of hypoproteinemia on pulmonary and soft tissue edema formation.

The effect of acute hypoproteinemia on the rate of fluid flux across the pulmonary and soft tissue microcirculation was studied in the unanesthetized sheep. Lymph flow was used to monitor fluid flux, a protein depletion of 30-50% of baseline value was produced by plasmapheresis. Vascular hydrostatic pressures and cardiac output were maintained constant with crystalloid infusion. The measured oncotic pressure in plasma, pi rho rapidly decreased as did the oncotic gradient between plasma and lymph. Lung and soft tissue lymph flow increased 2- to 3-fold immediately after protein depletion. Lung interstitial oncotic pressure, pi L, as measured in lymph, decreased to return the oncotic gradient and lymph flow to baseline by 24 h. Soft tissue oncotic gradient also returned to baseline by 24 h, but lymph flow remained significantly elevated for the next 48 h, indicating an increase in fluid flux unrelated to changes in oncotic pressure. Lymph flow rapidly returned to baseline when protein was returned. Protein depletion may alter the soft tissue interstitial matrix, allowing for edema formation. More effective mechanisms prevent this from occurring in the lung.

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

The effects of hypoproteinemia on blood-to-lymph fluid transport in sheep lung.

We studied the effects of reducing the plasma protein concentration on flow and composition of pulmonary lymph in 12 unanesthetized sheep. Whole blood was removed while red cells were returned and lactated Ringers was infused at a rate sufficient to maintain pulmonary vascular pressures at baseline values. A 44-54% reduction in plasma protein concentration resulted in a decrease in the plasma oncotic pressure from 18.6 +/- 1.1 to 7.8 +/- 0.9 mm Hg. Within an hour after plasmapheresis, lymph flows increased to a maximum of 4 times baseline. Subsequently, lymph flow gradually decreased and were close to baseline at 24 hours. The plasma-to-lymph oncotic gradient was reestablished in 5 hours due to decreased lymph protein. Maintained elevation of lymph flow with hydrostatic and oncotic gradients at baseline values suggest that the blood-to-lymph barrier offers less resistance to fluid transport. The calculated filtration coefficient increased 2- to 3-fold after plasmapheresis. Protein clearances remained normally coupled to lymph flows. Thus the enhanced fluid transport cannot be attributed to a permeability change in the large pore pathways. Hypoproteinemia may alter the interstitial gel so that there is less resistance to fluid movement. Such changes in fluid conductivity between blood capillaries and lymphatics may augment the lymphatic safety factor against pulmonary edema during hypoproteinemia.

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↗
PubMed1981

Endotoxin-induced lung injury in unanesthetized sheep: effect of methylprednisolone.

Our purpose was to study the effect of methylprednisolone (MPS) on endotoxin-induced lung injury. We used lung lymph flow and lymph protein content at sensitive indicators of pulmonary microvascular integrity in unanesthetized sheep. Seven animals were given E coli endotoxin (2 micrograms/kg) alone and also endotoxin with MPS pretreatment (30 mg/kg) in paired separate studies. The endotoxin injury was divided into an early hypertensive phase (30-90 minutes) characterized by a significant increase in pulmonary artery pressure (Ppa) and lymph flow, QL. This was followed later (3-5 hours) by a significant increase in protein-rich QL with normal pressures. MPS pretreatment significantly increased both injury phases in all animals. White cell count decreased in both groups; however, lymph beta-glucuronidase increased only in the nontreated group. Platelet count decreased in the nontreated group. Seven animals were then compared using endotoxin alone or with MPS treatment one hour after endotoxin. Only four of seven animals had a decrease in the lung injury after MPS treatment. We conclude that methylprednisolone is very effective in preventing lung injury, but only minimally effective in reversing the injury from endotoxin.

Animals↗
PubMed1981

Aspirin failure in symptomatic atherosclerotic carotid artery disease.

Over a 26-month period 27 urgent carotid endarterectomies were performed on patients who had been taking antiplatelet aggregating drugs for 6 months to 2 years. Angiography confirmed an original diagnosis of symptomatic extracranial carotid artery stenosis and ulceration in all patients. Nineteen had been started on dosages of aspirin from 325 to 1,300 mg/day, and eight started on aspirin plus persantine. Compliance to aspirin use appeared high. All had partial or total resolution of the ischemic symptoms after aspirin therapy was instituted. On readmission three patients had early stroke in evolution, and 24 had crescendo transient ischemic attacks. Reevaluation included cerebral angiography which confirmed progression of carotid artery disease to 90% or greater stenosis in each instance. All patients underwent successful carotid endarterectomies. A review of history of these 27 in the urgent group as opposed to the 45 symptomatic carotid patients who were electively operated on in the same time period revealed no significant (P greater than 0.10) differences in incidence of risk factors for atherosclerosis. However, none of the elective group had regularly taken aspirin. It would appear that aspirin decreased ischemic symptoms in the patients who underwent urgent operation by its antithromboxane effect, inhibiting platelet aggregation and embolization. However, aspirin appeared to have a deleterious effect on these patients by allowing their carotid disease to progress to a dangerous state by eliminating the symptoms of progressive carotid artery atherosclerosis or by accentuating the process of atherosclerosis possibly by inhibition of arterial prostacyclin.

Aged↗