Biomedical subjects
Publications and source records attributed to D J Deyo.
Those diseases that medicines do not cure, are cured by the knife, and those diseases that the knife cannot cure are cured by fire. And those diseases that fire does not cure are to be reckoned wholly incurable.
We tested the hypothesis that progressive aortic hypotension with bicarotid occlusion produces greater reductions in cerebral blood flow (CBF) and more flow-metabolism mismatching with hemodilution during cardiopulmonary bypass (CPB) than with hemodilution alone. In Yorkshire pigs randomized to hemodilution with CPB (n = 10) or hemodilution without CPB (control; n = 9), the effects of bicarotid ligation and graded hypotension on CBF (microspheres), the electroencephalogram (EEG), and cortical energy metabolites were examined. After bicarotid ligation, systemic flow was reduced for 15-min intervals of 80, 60, and 40 mm Hg aortic pressure, followed by a cortical brain biopsy. At baseline, CBF was lower in CPB (58 +/- 3 mL.100g-1.min-1) than control (90 +/- 3 mL.100 g-1.min-1., P < 0.05) animals, as was cerebral oxygen metabolism (3.1 +/- 0.1 vs 4.2 +/- 0.2 mL.min-1.100g-1; P < 0.05). Although CBF remained 40% lower at each level of hypotension in CPB than control animals (P < 0.05), EEG scores showed no intergroup differences, indicating similar flow-metabolism matching. Brain metabolites were similar between CPB and control groups (adenosine triphosphate, 9.6 +/- 2.4 vs 12.4 +/- 1.9 mumol/g; adenosine diphosphate, 6.0 +/- 0.7 vs 6.3 +/- 0.4 mumol/g; adenosine monophosphate, 4.8 +/- 0.9 vs 3.8 +/- 0.8 mumol/g; creatine phosphate, 8.3 +/- 1.8 vs 7.9 +/- 1.0 mumol/g; and lactate, 178.4 +/- 20.2 vs 150.8 +/- 13.9 mumol/g). Thus, despite significantly lower CBF during hypotension with bicarotid occlusion in hemodiluted animals during normothermic CPB, cortical electrical activity and the balance between flow and metabolism did not differ from those in control animals without CPB.
OBJECTIVE: To determine whether low-dose dopamine infusion (5 micrograms/kg/min) during cardiopulmonary bypass selectively increases perfusion to the kidney, splanchnic organs, and brain at low (45 mm Hg) as well as high (90 mm Hg) perfusion pressures. DESIGN: Randomized crossover trial. SETTING: Animal research laboratory in a university medical center. SUBJECTS: Ten female Yorkshire pigs (weight 29.9 +/- 1.2 kg). INTERVENTION: Anesthetized pigs were placed on normothermic cardiopulmonary bypass at a 100-mL/kg/min flow rate. After baseline measurements, the animal was subjected, in random sequence, to 15-min periods of low perfusion pressure (45 mm Hg), low perfusion pressure with dopamine (5 micrograms/kg/min), high perfusion pressure (90 mm Hg), and high perfusion pressure with dopamine. Regional perfusion (radioactive microspheres) was measured in tissue samples (2 to 10 g) from the renal cortex (outer two-third and inner one-third segments), stomach, duodenum, jejunum, ileum, colon, pancreas, and cerebral hemispheres. MEASUREMENTS AND MAIN RESULTS: Systemic perfusion pressure was altered by adjusting pump flow rate (r2 = .61; p < .05). In the kidney, cortical perfusion pressure increased from 178 +/- 16 mL/min/100 g at the low perfusion pressure to 399 +/- 23 mL/min/100 g at the high perfusion pressure (p < .05). Perfusion pressure augmentation increased the ratio of outer/inner renal cortical blood flow from 0.9 +/- 0.1 to 1.2 +/- 0.1 (p < .05). At each perfusion pressure, low-dose dopamine had no beneficial effect on renal perfusion or flow distribution. Similar results were found in the splanchnic organs, where regional perfusion was altered by perfusion pressure but not by dopamine. In contrast, neither changing perfusion pressure nor adding low-dose dopamine altered blood flow to the cerebral cortex. CONCLUSIONS: These data indicate that the lower autoregulatory limits of perfusion to the kidneys and splanchnic organs differ from those limits to the brain during normothermic bypass. Selective vasodilation from low-dose dopamine was not found in renal, splanchnic, or cerebral vascular beds. Increasing the perfusion pressure by pump flow, rather than by the addition of low-dose dopamine, enhanced renal and splanchnic but not cerebral blood flows during cardiopulmonary bypass.
The new Tec 6 desflurane vaporizer is an electrically heated, pressurized, electromechanically coupled dual-circuit blender. We hypothesized that carrier gas viscosity should affect the electromechanical coupling of the fresh gas and vapor circuits, and that desflurane output should vary with different carrier gases. In the first portion of the study, the performance of eight vaporizers was evaluated using a constant dial setting of 10% desflurane with four different carrier gases and three different fresh gas flow rates. In the second portion of the study, the carrier gas flow rate was maintained at 1, 5, or 10 L/min, and vaporizer output was analyzed at all integer dial settings from 1% to 18%. Vaporizer output was highest when oxygen was the carrier gas and lowest when nitrous oxide was the carrier gas. This effect was accentuated at low fresh gas flow rates and correlated with carrier gas viscosity. At a flow rate of 1.0 L/min with a constant dial setting of 10%, the averaged output from vaporizers was 10.3 +/- 0.66, 9.4 +/- 0.58, 8.7 +/- 0.52, and 8.1 +/- 0.44 vol% for 100% oxygen, air, 30% oxygen plus 70% nitrous oxide, and 100% nitrous oxide, respectively. With 100% nitrous oxide as the carrier gas at a flow rate of 1.0 L/min, the vaporizer delivered 2 vol% less than the dial setting at dial settings in excess of 12%. Differences between the analyzed concentration and the dial setting were most pronounced with high concentrations of nitrous oxide at low fresh gas flow rates.
An extracorporeal heparin removal device system (HRDS) based on plasma separation and affinity adsorption has been developed to reduce the risks of protamine-related adverse reactions. The heparin clearance profile of the HRDS was characterized by the first-order exponential depletion. A mathematical model was established to predict the time to achieve 85% heparin removal for different body weights at 700 ml/min and 1400 ml/min extracorporeal HRDS blood flow. With an HRDS flow of 700 ml, 85% of total body heparin removal cannot be achieved within 30 min for subjects greater than 50 kg. With an HRDS flow of 1400 ml/min, 85% heparin removal can be achieved within 32 min for subjects larger than 90 kg. Such model predictions were validated in an adult swine (n = 10) model of 60-min, hypothermic (28 degrees C) cardiopulmonary bypass (CPB). Animals were given 300 U/kg intravenous heparin and 5000 U heparin in the circuit prime for initial heparinization, with subsequent heparin given to maintain activated clotting time above 450 sec. Immediately following CPB, plasma heparin concentration as determined by anti-factor Xa assays was 4.40 +/- 1.08 U/ml in the 700 ml/min group and 4.78 +/- 0.70 U/ml in the 1400 ml/min groups, respectively (p > 0.05). Target HRDS flow was 700 ml/min for animals below 75 kg and 1400 ml/min for animals above 75 kg. The mean body weight in the 1400 ml/min group (81.4 +/- 3.7 kg) was significantly higher than that in the 700 ml/min group (67.2 +/- 2.2 kg) (p < 0.05), with the actually achieved HRDS flow 658.5 +/- 20.8 and 1437.4 +/- 30.1 ml/min, respectively. During the HRDS run, plasma heparin concentration followed the predicted first-order exponential depletion (r2 = 0.97 for the 700 ml/min group and r2 = 0.99 for the 1400 ml/min group). In the 700 ml/min group, the time needed to achieve 85% heparin clearance was over 40 min, whereas in the 1400 ml/min group, this time was reduced to less than 30 min despite greater body weight. At 30 min on HRDS, the 700 ml/min group had 27.4 +/- 3.7% heparin left in the plasma, whereas the 1400 ml/min group had only 12.6 +/- 2.5% (p < 0.05). The authors conclude heparin clearance by the HRDS can be precisely predicted with the mathematical model of first-order exponential depletion. Increasing the HRDS flow can effectively reduce the time needed to achieve a targeted heparin removal.
The heparin removal device (HRD), using plasma separation and poly-L-lysine (PLL) affinity adsorption, has been shown to be an effective alternative to protamine after cardiopulmonary bypass (CPB). Previous designs of the HRD used standard Luer-Lok ((phi = 2.3 mm) port connections between the extracorporeal tubing and the plasma separation chambers, which resulted in excessively high circuit pressures (> 750 mm Hg) at an HRD flow of 1,400 ml/min. To reduce circuit pressures, we enlarged the connection ports to phi = 4.2 mm, keeping other circuit components and sorbent amounts unchanged. The modified circuit HRD was divided into the SMALL PORT group (phi = 2.3 mm, A = 4.15 mm2) and the LARGE PORT group (phi = 4.2 mm, A = 13.85 mm2) in adult swine (70+/-5 kg) given 300 U/kg heparin. A dual lumen cannula was inserted into the right atrium and connected to the HRD. Inlet pressure ranged from 749+/-42 to 795+/-57 mm Hg in the SMALL PORT group during the HRD run at 1,400 ml/min, whereas it ranged from 345+/-5 to 372+/-34 mm Hg in the LARGE PORT group (p < 0.01 between groups). Likewise, the chamber pressure ranged from 447+/-21 to 452+/-27 mm Hg in the SMALL PORT group and from 190+/-14 to 204+/-19 mm Hg in the LARGE PORT group (p < 0.01 between groups). There were no significant differences in ACT between groups. We conclude that enlarged chamber ports significantly lower circuit pressures for the HRD without changing heparin removal capability.
Our group is developing an artificial lung as a bridge to transplant. We evaluated the sheep pulmonary artery (PA) for the presence or absence of a septum, which may increase PA resistance and affect artificial lung flow. We also measured the PA size to determine whether it is a suitable conduit for artificial lung implantation using a PA-PA shunt. Adult Suffolk ewes in two groups were studied. Group 1 consisted of animals (n = 12, 30-43 kg) prepared for thoracotomy. Group 2 (n = 21, 30-43 kg) consisted of postmortem dissections. In both groups, the length and girth of the PA was measured. The heart and lungs were removed on all postmortem animals (group 2), the ductus arteriosum was crosscut, and the common PA was incised. The average length of the PA in live animals was 5.5 cm and the average diameter was 2.2 cm. The average length of the PA in postmortem animals was 4.8 cm and the average diameter was 2.0 cm. All pulmonary arteries were aseptate, and the ligamentum arteriosum in each PA was not patent. We conclude that the PA is not a source of increased resistance and is a suitable conduit for artificial lung implantation in the PA-PA configuration.
To evaluate the ability of arteriovenous carbon dioxide removal (AVCO2R) to maintain hemodynamic stability during treatment of adult respiratory distress syndrome (ARDS), we used our smoke/burn, LD40 sheep model of ARDS. With onset of ARDS (PaO2/FiO2 < 200) animals were randomized to AVCO2R (n = 20) or SHAM (n = 8). With AVCO2R, the carotid artery (10-14 F) and jugular vein (14-16 F) were cannulated; SHAM received identical management, sparing the vessels. AVCO2R maintained stable hemodynamics compared to SHAM at 48 hours; heart rate (114.8+/-6.1 vs. 110.1+/-11.0 beats/min.), mean arterial pressure (112+/-5.1 vs. 107.0+/-8.5 mm Hg), cardiac output (7.4+/-0.5 vs. 7.5+/-0.9 L/min.), pulmonary arterial pressure (26+/-2.4 vs. 21+/-1.3 mm Hg), pulmonary arterial wedge pressure (14.1+/-1.8 vs. 14.0+/-1.2 mm Hg), and central venous pressure (7+/-1.6 vs. 8+/-0.9 mm Hg). At 48 hours, AVCO2R allowed significant reductions (p<0.05) in minute ventilation (13.6+/-2.5 to 7.6+/-0.8 L/min); tidal volume (TV) (389.4+/-24.1 to 295.0+/-10.1 ml); peak inspiratory pressure (PIP) (25.4+/-9.2 to 18.8+/-2.5 cm H2O); RR (27.5+/-0.7 to 21.6+/-1.8 breaths/min); and FiO2 (0.96+/-0.00 to 0.48+/-0.2) while normocapnia was maintained. AVCO2R is an effective method of CO2 removal during severe respiratory failure that is hemodynamically well tolerated.
The goal was to develop a clinically relevant animal model that could be used to assess the efficacy of therapeutic interventions in lung cancer. Two cell lines, noncancerous control (BEAS2-B, immortalized human bronchial-epithelial cell line) and cancerous (BZR-T33, H-ras transformed BEAS2-B) were implanted into nude (athymic) mice. Two groups (n = 10 each) received dorsoscapular subcutaneous injection of 10(6) cells from either cell line. BEAS2-B cells were nontumorigenic, whereas mice with BZR-T33 cells had tumors (9,510 +/- 4,307 mm3) confirmed by histology, and a significantly smaller body weight (BZR-T33, 28.5 +/- 0.49 vs. BEAS2-B, 30.7 +/- 0.75 g, p < .05). The next phase evaluated invasion/metastasis. Two groups (n = 10 each) received 10(6) cells from either cell line injected into tail veins. Animals receiving BZR-T33 cells had a smaller body weight, palpable lung masses (67%), obvious tail masses (44%), and average tumor burden (1,120 +/- 115 mm3), and histology revealed invasion of lung tissue and interstitial hemorrhage. In development of the orthotopic xenotransplanted model, mice (2 groups, n = 10 each) received 10(6) cells from either cell line implanted into the lungs through a tracheotomy. Animals with BZR-T33 cells did not survive past 59 days and had a smaller body weight, increased lung weight, lung masses (100%), and metastatic loci (30%). Magnetic resonance imaging (MRI) confirmed the presence of masses in intubated live mice, later confirmed by histology. In summary, the H-ras transfected cell line developed lung masses following tail-vein injection and endotracheal seeding. Evaluation by MRI allows for a comprehensive model with significant potential in the study of lung cancer.
Whole-body hyperthermia is currently under investigation as a method to treat systemic malignancies; however, available techniques induce a derangement in serum and urine chemistries. This study was done to determine whether veno-venous perfusion induced hyperthermia (vv-PISH) that incorporated a parallel dialysis system to control blood chemistries would eliminate these heat induced derangements. Adult female Yorkshire swine were divided into perfusion only (group P, n = 6, 62.8 +/- 2.5 kg), and perfusion with dialysis (group PD, n = 6, 63.8 +/- 4.3 kg). In both groups, hyperthermia was induced with a computer assisted jugular-to-femoral venovenous heat exchange/perfusion system primed with a balanced electrolyte solution, operating at 30 ml/min-1/kg-1, which used a thermal gradient induced by blood heated to a maximum of 48 degrees C and a perfusate-to-blood temperature gradient < 10 degrees C during heating. The target core temperature was 43 degrees C for 120 min as measured by the average of the rectal, bladder, esophageal, bilateral tympanic, and pulmonary artery temperatures. Including ramp-up and cool down, the total perfusion interval was 263 +/- 29 min in group P and 240 +/- 18 min in group PD (ns). Serum and urine chemistry values expressed as the mean value +/- SEM were compared before and after hyperthermia treatment. Variables include blood urea nitrogen, creatinine, sodium, potassium, chloride, calcium, magnesium, phosphorus, glucose, total protein, albumin, alkaline phosphatase (ALKP), creatinine kinase, aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), plasma free hemoglobin, urine specific gravity, pH and urine creatinine. All variables remained within normal ranges for the PD group. In the P group, the following final values were outside the normal range: (normal range) creatinine 2.1 +/- 1 (0.4-1.4) mg/dl, Ca2+ 5.1 +/- 1 (6-13) mg/dl, Mg2+ .8 +/- 0.1 (1.2-10) mg/dl, ALKP 134 +/- 6 (34-122) U/L, ALT 69 +/- 3 (9-51) U/L, and LDH 1291 +/- 237 (300-600) U/L. We conclude that the significant changes in serum and urine chemistries associated with vv-PISH are normalized with the use of a parallel dialysis system and may decrease the incidence of electrolyte associated complications.
To reduce the risks of protamine reactions after cardiopulmonary bypass (CPB), a heparin removal device (HRD) with plasma separation and poly-L-lysine (PLL) affinity adsorption was developed. To compare the efficacy of HRD with that of protamine, blood coagulation variables were evaluated in a swine model of CPB. Female Yorkshire swine were randomly divided into the HRD group (n = 6, weight 79.7 +/- 7.0 kg) and the protamine group (n = 6, weight 79.3 +/- 6.8 kg), and subjected to 60 min of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual lumen cannula in the HRD group. Blood flow was drained from the inferior vena cava, through the plasma separation chamber of the HRD where heparin was bound to PLL, and re-infused into the right atrium. The HRD run time was determined by an established mathematical model of first-order exponential depletion targeted to 90% heparin removal. In the protamine group, protamine was given in a 100 U heparin to 1 mg protamine ratio after CPB in a slow intravenous infusion. Hemodynamics, activated clotting time (ACT), activated partial thromboplastin time (APTT), and heparin concentration were obtained before, every 5 min during, and after the use of the HRD or before and after protamine administration, and 1 and 3 hours after HRD or protamine. Heparin concentration immediately after CPB was 4.90 +/- 0.19 U/ml in the HRD group and 3.94 +/- 0.63 U/ml in the protamine group, respectively (p > 0.05 between groups). The ACT was 994 +/- 7 sec in the HRD group and 768 +/- 55 sec in the protamine group, and APTT was greater than 150 sec in both groups (p > 0.05 between groups). In the HRD group, the HRD run time was determined to be 31.5 +/- 2.4 min for the targeted 90% heparin removal, and the plasma heparin concentration followed first-order depletion kinetics. In the protamine group, the full dose of protamine was administered over 15 min. Immediately after the HRD run or protamine administration, plasma heparin concentration decreased to 0.48 +/- 0.09 U/ml in the HRD group and 0.13 +/- 0.02 U/ml in the protamine group (p < 0.01 between groups); likewise, ACT decreased to 188 +/- 25 sec in the HRD group and 101 +/- 5 in the protamine group (p < 0.01 between groups). The APTT was not significantly different between the groups at any time during the experiment. Plasma heparin concentration and ACT were not significantly different three hours after the HRD run or protamine administration. The authors conclude that the HRD is capable of predictable reversal of systemic heparinization after CPB, and is an alternative to achieve heparin clearance in subjects who may develop adverse reactions to protamine.