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Biomedical subjects

R A Gunther

Publications and source records attributed to R A Gunther.

At least 37 records · Page 2Linked to original sources
PubMed1992

Intraperitoneal carbon dioxide insufflation and cardiopulmonary functions. Laparoscopic cholecystectomy in pigs.

We studied the effects of laparoscopic cholecystectomy on respiratory and hemodynamic function in eight adult pigs. Minute ventilation was adjusted to normalize baseline arterial blood gases, then fixed throughout carbon dioxide insufflation. A metabolic measurement cart recorded total CO2 excretion, oxygen consumption, and minute ventilation. Carbon dioxide pneumoperitoneum was maintained at a constant pressure of 15 mm Hg as cholecystectomy was performed. After 1 hour of insufflation, CO2 excretion increased from 115 +/- 10 mL/min to 149 +/- 9 mL/min but O2 consumption remained unchanged. The PaCO2 increased from 35 +/- 2 mm Hg to 49 +/- 3 mm Hg and arterial pH fell from 7.47 +/- 0.02 to 7.35 +/- 0.03. Systemic and pulmonary hypertension occurred and stroke volume dropped from 35.5 +/- 3.5 mL to 28.6 +/- 2.2 mL with compensatory tachycardia. Right atrial pressure remained unchanged as inferior vena cava pressure increased to reflect the intraperitoneal pressure. We conclude that CO2 pneumoperitoneum resulted in significant transperitoneal CO2 absorption, with secondary hypercapnia and acidemia. The accumulation of CO2 was also associated with an increase in systemic and pulmonary arterial pressure. Heart rate increased to compensate for the decreased stroke volume to maintain cardiac output.

Acid-Base Equilibrium↗
PubMed1992

Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow.

Recently, we have shown that exposure of intubated conscious sheep to 3 to 4 ppm ozone (O3) for 3 h increases bronchial blood flow (Qbr). The purpose of the present study was to assess the potential role of corticosteroids in modulating this increase. Six nasally intubated sheep were exposed to filtered room air, 3.5 ppm O3 on two separate occasions, and 3.5 ppm O3 plus methyl-prednisone, for 3 h. Qbr was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored. After 3 h of 3.5 ppm O3, Qbr increased from 3.2 +/- 0.5 (mean +/- SEM) to 8.5 +/- 1.6 KHz, whereas bronchial vascular resistance (BVR) decreased from the baseline value of 43.6 +/- 8.0 to 15.0 +/- 3 mm Hg/KHz. With corticosteroids, baseline Qbr was 3.2 +/- 0.6 and BVR was 44.2 +/- 9.7; after 3 h of 3.5 ppm O3, Qbr was 3.3 +/- 0.5 KHz and BVR was 39.0 +/- 8.0 mm Hg/KHz. The two 3.5-ppm O3 exposures without corticosteroids were impressively reproducible. Except for Qbr and BVR, no other measured cardiovascular parameters were affected by O3. The results indicate that corticosteroids are capable of interfering with mediator, neurohumoral, or inflammatory cell mechanisms responsible for vasodilation of the airway microcirculation after O3 exposure, but do not specifically address the specific processes whereby this attenuation occurs.

Analysis of Variance↗
PubMed1991

Marked increase of plasma hyaluronan after major thermal injury and infusion therapy.

Hyaluronan (HYA) is an important structural element in skin and is presumably participating in regulation of the interstitial fluid volume. HYA is transported via the lymphatics from the tissues to the blood, where its concentration is normally very low. Fluid flux through the interstitium is markedly increased after thermal injury. The present study was performed to determine whether major thermal injury would affect plasma levels of HYA. In halothane-anesthetized sheep subjected to 40% BSA full-thickness scald burns, plasma HYA concentration increased from 116 +/- 19 (mean +/- SEM) to 172 +/- 18 ng/ml within 1 hr after injury (P less than 0.05). After 3 hr of fluid therapy plasma HYA concentration was further elevated to 10 times baseline (1417 +/- 322 ng/ml) (P less than 0.01). To clarify whether this rise represented an increased "washout" of interstitial HYA, attributable either to the burn injury or the subsequent fluid therapy, awake sheep were subjected to overhydration. Following a 3-hr infusion of lactated Ringer's 2.5 liter/hr, plasma HYA concentration increased to 2-3 times baseline. Lung lymph flow and its concentration of HYA increased, leading to an increase in the lymphatic flux of HYA to 10-20 times baseline. In peripheral lymph HYA flux increased 2-3 times baseline. Infusion of lactated Ringer's markedly increased lymphatic removal of HYA. However, plasma concentrations of HYA were 3 times higher after thermal injury than following fluid challenge alone, suggesting that thermal injury per se may also increase input of HYA into the systemic circulation.

Animals↗
PubMed1991

Dose response characteristics of hypertonic saline dextran solutions.

In an effort to find the best hypertonic saline-dextran solution (HSD) for prehospital use, 33 chronically catheterized sheep were bled using a fixed pressure shock model (50 mm Hg x 2 hours) and resuscitated with 4 ml/kg of HSD solution (2-minute bolus). In the first set of experiments colloid was varied and sodium chloride was held constant, as 7.5% NaCl was paired with either 0%, 6%, or 12% dextran 70. A dose-response relationship existed, with cardiac output increasing 20% with each sequential dextran 70 concentration. Mean arterial blood pressure was higher in animals that were resuscitated with either the 7.5% NaCl/6% dextran 70 or 7.5% NaCl/12% dextran 70 solution (p less than 0.05). Using the optimal dextran 70 concentration from the first set of experiments (i.e., 12%), solute was varied in a second set of experiments comparing 0.9%, 3.8%, 7.5%, or 10% NaCl/12% dextran 70. Again, dose-response features were demonstrated, as cardiac output increased as a function of NaCl concentration. However, this response plateaued with the 7.5% NaCl concentration and no advantage was obtained by increasing the NaCl concentration to 10%. We conclude that a 4-ml/kg bolus of 7.5% NaCl/12% dextran 70 solution may be a more effective form of therapy than those previously evaluated. This new solution is now being included in our ongoing clinical trials.

Animals↗
PubMed1991

Effects of recombinant human interleukin-2 and excipient infusion on plasma levels of prostaglandins and thromboxane B2 in sheep.

Systemic administration of recombinant human interleukin-2 (rIL-2) is used for treating some patients with advanced cancer. This therapy is limited by severe adverse reactions of cardiovascular and gastrointestinal origin. The effects of rIL-2 treatment on plasma levels of some prostanoids were examined in sheep in order to elucidate the mechanism of these adverse reactions. A total of 8 adult female Suffolk sheep were used. rIL-2 (0.1 mg/kg) was infused over a 30-min period in 4 sheep. Four different sheep in the control group received an excipient, which consisted of 5% mannitol and sodium dodecyl sulfate (SDS) (187 micrograms SDS/mg rIL-2), in the same way. Plasma levels of prostaglandin (PG) F2 alpha in rIL-2-treated animals showed significant increases from 1.5 to 6 h over the excipient treated animals with a maximal increase of 138% of the pooled zero time control value (p less than or equal to 0.01) at 6 h. The pooled zero time control plasma PGF2 alpha concentration was 443.0 +/- 45.9 pg/ml. Plasma levels of 6-keto-PGF1 alpha in rIL-2-treated animals showed a significant increase (p less than or equal to 0.02) over the excipient treated animals at 0.5 h but the value was only 103% of the pooled zero time control. Plasma levels of 6-keto-PGF1 alpha in excipient-treated animals showed a maximal increase of 156% of the pooled zero time control value (55.6 +/- 8.9 pg/ml) at 5 h and it was significantly higher than the rIL-2-treated sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Acute ozone exposure increases bronchial blood flow in conscious sheep.

This study was initiated to determine the effects of ozone (O3) on sheep airway blood flow. Twenty-three nasally intubated sheep were exposed to filtered air (n = 5), 1 ppm O3 (n = 4), 2 ppm O3 (n = 5), 3 ppm O3 (n = 5), and 4 ppm O3 (n = 4) for 3 h. Bronchial artery flow (Qbr) was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored during the period of the exposures. Exposure to 3 and 4 ppm O3 resulted in a significant increase in Qbr (103 and 204% change, respectively) without affecting any of the other cardiopulmonary parameters measured. These results indicate that O3 induces a dose dependent increase in Qbr which is the result of a vasodilation of the bronchial vasculature which is not dependent upon changes in blood gases or upstream driving pressure.

Administration, Intranasal↗
PubMed1990

Evaluation of an intraosseous infusion device for the resuscitation of hypovolemic shock.

An intraosseous infusion device designed for the prehospital administration of hypertonic saline-dextran solutions was evaluated by resuscitating hemorrhaged conscious sheep. Eight animals underwent 2 hours of hemorrhagic hypotension (50 mm Hg, bled volume = 43 +/- 7 ml/kg). This was followed by the intraosseous infusion of 200 ml (4-5 ml/kg) of 7.5% NaCl-6% dextran 70 into the bone marrow of the sternum. Results were compared to seven control animals (bled volume = 31 +/- 6 ml/kg) resuscitated through a central venous catheter. Despite the small volumes infused, mean arterial blood pressure and cardiac output were rapidly normalized in both groups by 10 minutes post resuscitation (p less than 0.01). Plasma sodium concentration increased an average of 12 mEq/L and plasma volume was rapidly expanded regardless of route. The metabolic acidosis of hemorrhagic shock was rapidly corrected, pulmonary pressures remained normal, and hypoxemia did not occur after intraosseous resuscitation. The device provided safe and rapid vascular access via the sternal bone marrow space. The use of intraosseous infusion of hypertonic saline dextran solutions via the sternal bone marrow may allow prehospital rescuers to consistently incorporate fluid replacement therapy into 'scoop and run' policies by avoiding the time delays associated with failures in IV access.

Animals↗
PubMed1990

Effectiveness of hypertonic saline-dextran 70 for initial fluid resuscitation of major burns.

Small-volume resuscitation (4 ml/kg) with hypertonic saline-dextran (HSD) has been shown effective in hemorrhagic shock. In the present study the effectiveness of an initial 4 ml/kg bolus infusion of HSD on cardiovascular function and fluid resuscitation requirements after a major burn injury was evaluated in anesthetized sheep following a 40% BSA scald burn. One hour after injury resuscitation was initiated by a rapid intravenous bolus infusion (4 ml/kg) of either hypertonic saline-dextran (7.5% NaCl in 6% dextran 70) (HSD) or the same volume of normal (isotonic) saline (NS). Lactated Ringer's was later infused as needed to maintain cardiac output at 90% of baseline. HSD rapidly and effectively restored cardiac output and mean arterial pressure significantly better than the same volume of NS. Hemodynamic improvement by HSD was short lived, and need for further fluid therapy was only marginally delayed (HSD 38 +/- 8 min, NS 20 +/- 3 min; p = 0.06) (mean +/- SEM). The total requirements for fluid therapy during the first 6 hr postburn were not reduced by the initial HSD bolus (HSD 3,145 +/- 605 ml, NS 2,905 +/- 495 ml; n.s.), nor was skin edema formation reduced. We conclude that in anesthetized sheep HSD resuscitation was only transiently effective in treating burn shock. This may be attributed to the sustained increase in vascular permeability and continued plasma leak following thermal injury.

Animals↗
PubMed1990

Steroid pretreatment reduces interleukin-2 toxicity in sheep.

Recombinant interleukin-2 (rIL-2) has shown promise in the treatment of patients with advanced cancer. However, toxicity of this therapy remains a major problem with its use in some patients. In this study we examined whether steroids could reduce the adverse cardiopulmonary effects of rIL-2. Seven sheep were surgically prepared with vascular catheters and lung lymph fistulas. Each sheep received either a single dose of rIL-2 (100 micrograms/kg) or rIL-2 plus methylprednisolone (30 mg/kg) followed by the reverse treatment 1 week later. Lung lymph flow increased markedly after rIL-2 with a peak QL of 140% +/- 30% (above baseline). Steroid pretreatment significantly reduced this lymph flow increase with peak lung lymph flow being only 40% +/- 16% (p less than 0.004). The lymph/plasma protein ratio tended to increase after rIL-2, but these changes were not statistically significant. After rIL-2, cardiac output, heart rate, core temperature, and mean pulmonary artery pressure increased (p less than 0.05), whereas systemic vascular resistance and arterial PO2 decreased (p less than 0.05). These changes did not occur with steroid pretreatment. The results of this study demonstrate that steroids reduced the adverse cardiopulmonary effects of rIL-2. We believe that rIL-2 induces activation of arachidonic acid metabolism, which leads to the production of multiple inflammatory mediators that cause increased microvascular permeability and the adverse cardiopulmonary effects of rIL-2.

Animals↗
PubMed1989

In vivo biology of recombinant interleukin-2 infusion in sheep: cardiopulmonary manifestations of an intravascular immune-inflammatory response.

We have described the physiologic changes that occur in the conscious sheep during five days of dosing with rIL-2. Major effects noted were a decrease in systemic vascular resistance (vasodilation) accompanied by an increase in cardiac output (blood flow) and heart rate and a mild increase in pulmonary vascular resistance (vasoconstriction). Body temperature increased and may have contributed to the peripheral vasodilation. Lung microvascular fluid and protein flux increased following rIL-2 administration, as evidenced by an increase in lung lymph flow and protein clearance, and circulating levels of leukocytes decreased. These phenomena were temporally related. Since the composite biologic response that occurred following rIL-2 administration was characterized by changes in vascular caliber and blood flow, increased vascular permeability, and margination of leukocytes, we propose that the response be viewed as an intravascular inflammatory reaction.

Animals↗
PubMed1989

Ozone-induced accelerated lung clearance of 99mTc-DTPA aerosol in conscious sheep.

This study was initiated to determine the rate and characteristics of 99mTc-DTPA clearance from the lungs of unanesthetized sheep exposed to varying concentrations of O3 for 4 h in a whole-body exposure chamber. Four sheep exposed to 1 ppm O3 had a monoexponential T50 of 274 +/- 81 min (SD), not significantly different from sham exposures (316 +/- 150); 5 sheep exposed to 2 ppm had a T50 of 234 +/- 101 min, not significantly different from sham exposures (364 +/- 131 min). Five additional unanesthetized sheep exposed to 2 ppm for 4 h via a nasotracheal tube had a T50 of 192 +/- 55 min, significantly different from sham exposures (300 +/- 96 min). The results show that the effect of oxidant pollutants on the permeability of alveolobronchiolar epithelium may be assessed in conscious sheep.

Aerosols↗
PubMed1989

Comparison of hypertonic saline/dextran versus hypertonic saline/hetastarch for resuscitation of hypovolemia.

In the present study, we compare resuscitation of bled sheep with hypertonic saline/dextran or hypertonic saline/hetastarch. Unanesthetized sheep were subjected to 2 h of hemorrhagic hypotension and then resuscitated with 200 ml of 7.5% NaCl solution made up to include either 6% dextran 70 (Macrodex) or 6% hetastarch (Hespan). Both solutions provided an immediate and sustained improvement in arterial pressure and cardiac output. The hypertonic saline/dextran provided a slightly better overall response as mean arterial pressure, cardiac output and central venous pressure were higher in the dextran group at all times post resuscitation. However, only the differences in arterial pressure and initial plasma volume expansion were statistically significant. The somewhat better response to hypertonic saline/dextran may be explained by the higher oncotic pressures generated by dextran compared to equal concentrations of hetastarch.

Animals↗
PubMed1989

Resuscitation of hemorrhage with intraosseous infusion of hypertonic saline/dextran.

We resuscitated unanesthetized bled sheep (bled volume = 1.2-1.7 liters) with 200 ml of hypertonic saline/dextran 70 infused either through a peripheral vein (n = 6) or directly into the red marrow of the sternum (n = 6). Intraosseous infusion of the viscous 7.5% NaCl/6% dextran solution required 2-4 min. Plasma sodium was rapidly increased to the same level in both groups demonstrating equally rapid entry into the vascular space. Both regimens provide rapid and sustained normalization of arterial pressure and cardiac output. No significant differences between the two groups were apparent for any measured variable. Intraosseous infusion of hypertonic resuscitation fluids merits further research to evaluate the safety and efficacy for prehospital treatment of hypovolemia and trauma.

Animals↗
PubMed1988

Lung clearance of 99mTc-DTPA aerosol in conscious sheep.

This study was initiated to determine the rate and characteristics of 99mTc-DTPA clearance from the whole lung in a group of 9 sheep. Submicronic aerosol droplets were delivered to unsedated sheep held in a sling-like frame. Best fits for clearance curves to single- and biexponentials were calculated. The monoexponential T50 for the aerosol clearance was 293 min +/- 74 SD. Background correction was found to have a minimal effect (approx. 10%). Biexponential fitting only marginally improved correlations in the 8 healthy sheep, but in one additional animal with clinical evidence of pneumonia, clearance was faster and biexponential fitting was substantially better. These clearance values in conscious sheep are longer than previous findings with 99mTc-DTPA in anesthetized sheep. There appears to be a wide variation of radioaerosol 99mTc-DTPA lung clearances among different species, sheep exhibiting a comparatively prolonged clearance profile.

Administration, Inhalation↗
PubMed1987

Clearance of instilled surfactant lipid from the lungs of unanesthetized sheep: lipids are differentially transported by nonlymphatic pathways.

The routes used by the lung to dispose of instilled exogenous surfactant lipid components were examined with the sheep chronic lung lymph fistula preparation. Small vesicles of radiolabeled dipalmitoyl phosphatidylcholine (DPPC) either alone or with radiolabeled cholesterol (CHOL) were instilled intratracheally, and samples of lung lymph and plasma were collected at 60-minute intervals for 12 hours. At any time point, the total amounts of either labeled DPPC or CHOL that appeared in lung lymph were small fractions (less than 0.5%) of their respective amounts in plasma. Labeled DPPC, as DPPC alone or as DPPC/CHOL (2:1 molar ratio), appeared simultaneously in plasma and lymph and displayed the same time course of appearance regardless of vesicle composition. CHOL appearance was also simultaneous in both plasma and lymph, but was distinctly slower than that of DPPC. The time differences noted between the appearance of labeled DPPC and CHOL in lymph and plasma indicate that these two lipid components of the instilled surfactant lipid component vesicles appear to be handled in different fashions during their transport from the lung. Further, the data obtained by sampling lung lymph suggest that the lung interstitial space may not play an active role in the transport of exogenously administered lipid from the lung.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1986

Small-volume resuscitation with hypertonic saline dextran solution.

Small-volume hypertonic resuscitation has been proposed as an effective means for restoration of cardiovascular function after hemorrhage at the scene of an accident. We evaluated the cardiovascular, metabolic, and neurohumoral response of resuscitation after hemorrhage using 200 ml of 2400 mosm sodium chloride, 6% dextran 70. Unanesthetized adult sheep were bled to maintain mean arterial pressure at 50 mm Hg for 3 hours, shed blood volume = 42 +/- 7 ml/kg. The sheep were then treated with a single bolus infusion of hypertonic saline dextran (n = 7) or normal saline solution (control group, n = 7) and then observed for a 30-minute period of simulated patient transport during which no additional fluid was given. Hypertonic saline dextran caused rapid restoration of blood pressure and cardiac output within 2 minutes of infusion. Cardiac output remained at or above baseline level, while both O2 consumption and urine output increased to above baseline level during the 30 minutes of simulated patient transport. By comparison 200 ml of normal saline solution caused only a small increase in blood pressure and no improvement in cardiac output or oxygen consumption. After this 30-minute period, both groups were given lactated Ringer's solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringer's solution required to maintain cardiac output was less in the hypertonic group, 371 +/- 168 ml, only one sixth that of the control group, 2200 +/- 814 ml. In summary after 3 hours of hypovolemia, a small volume of hypertonic saline dextran, about 4 ml/kg, fully restored cardiovascular and metabolic function for at least 30 minutes and significantly lowered the total volume requirements of resuscitation.

Animals↗
PubMed1985

A comparison of several hypertonic solutions for resuscitation of bled sheep.

Small volumes (4 ml/kg) of 2400 mOsm NaCl restore cardiac output and mean arterial pressure to 80% of baseline after hemorrhage (65% of blood volume) in unanesthetized sheep. An equal volume of normal saline is less effective. To identify an optimal hypertonic solution, we screened six 2400 mOsm solutions in 18 randomized experiments in 8 sheep: NaCl, NaHCO3, NaCl/sodium acetate, NaCl/mannitol, NaCl/6% Dextran 70, and glucose. Cardiovascular function, as determined by cardiac output and mean arterial pressure, was restored best with NaCl, NaCl/NaAc, and NaCl/Dex. These three solutions were then evaluated using 18 sheep in 36 experiments. Following a 1-hr baseline period, the sheep were bled to a mean arterial pressure of 50 mm Hg for 2 hr. One of the solutions was then given in a volume of 4 ml/kg over 2 min and the sheep were monitored for 3 hr. Within 3 min of the infusion, cardiac output increased to greater than 100% of baseline for all three solutions. The NaCl-Dex solution sustained a significantly higher cardiac output over the 3-hr observation period than the other solutions. Plasma volume increased for all solutions following infusion. NaCl-Dex maintained plasma volume significantly better than the other solutions. As a further control, an isotonic solution of 6% Dextran 70 in normal saline was studied. It was not as effective as the hypertonic NaCl-Dex in maintaining cardiac output, mean arterial pressure, or plasma volume. Osmolality increased 10% (309 to 326 mOsm/kg H2O), plasma [NA] increased 7% (151 to 161 meq/liter), and plasma [K] decreased from 3.9 to 2.6 meq/liter following the hypertonic infusions. The sheep appeared to tolerate these electrolyte changes well. We conclude that a single bolus infusion of 2400 mOsm NaCl with 6% Dextran 70 best resuscitates sheep that have been subjected to a moderate degree of hemorrhagic shock compared to several other solutions. Its beneficial effects are caused in part by a sustained reestablishment of plasma volume. More studies are needed to document the safety of dextran in the clinical setting of hemorrhagic shock. Small volumes of hypertonic solutions may be valuable in the initial fluid resuscitation of patients in hemorrhagic shock.

Animals↗