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Biomedical subjects

R A Vertrees

Publications and source records attributed to R A Vertrees.

At least 19 recordsLinked to original sources
PubMed2001

Safety and efficacy of a heparin removal device: a prospective randomized preclinical outcomes study.

BACKGROUND: Systemic protamine sulfate for heparin reversal after cardiopulmonary bypass (CPB) is associated with uncommon, but life-threatening adverse reactions. METHODS: In a prospective randomized 3-day outcomes study, a heparin removal device (HRD) group (n = 12; 60-, 80-, 100-kg subgroups) was compared with a matched systemic Protamine group (Protamine; n = 6) for safety and efficacy using an adult swine model of CPB (60 minutes, 28 degrees C). RESULTS: HRD run time was 25 to 38 minutes depending on weight without complications. After HRD, heparin concentration decreased from 4.77 +/- 0.17 to 0.45 +/- 0.06 U/mL (activated clotting time [ACT] 776 +/- 83 to 180 +/- 12 seconds), and in Protamine, 3.94 +/- 0.63 to 0.13 +/- 0.02 U/mL (ACT 694 +/- 132 to 101 +/- 5 seconds) (p = 0.01 between groups, but no significant differences 60 minutes later). No significant difference between HRD and Protamine to 72 hours was seen in plasma-free hemoglobin C3a, heparin concentration, thromboelastogram index, platelet count, activated partial thromboplastin time, anti-thrombin III, fibrinogen, ACT, and tissue histology. CONCLUSIONS: In a prospective randomized outcomes study, HRD achieved predictable reversal of systemic heparinization after CPB with no difference in safety or outcomes compared with protamine.

Adsorption↗
PubMed2001

Percutaneous venovenous perfusion-induced systemic hyperthermia for advanced non-small cell lung cancer: initial clinical experience.

BACKGROUND: Venovenous perfusion-induced systemic hyperthermia raises core body temperature by extracorporeal heating of the blood. Five patients with advanced non-small cell lung carcinoma stage IV (4.4+/-1 months after initial diagnosis) received venovenous perfusion-induced systemic hyperthermia to 42.5 degrees C (core temperature) to assess technical and patient risks. METHODS: After general anesthesia and systemic heparinization (activated clotting time > 300 seconds), percutaneous cannulation of the right internal jugular vein (15F) for drainage and common femoral vein (15F) for reinfusion allowed extracorporeal flow rates up to 1,500 mL/min (20 mL x kg(-1) x min(-1)) with the ThermoChem System. This device uses charcoal-based sorbent for electrolyte homeostasis. Six monitored sites (rectal, bladder, tympanic x2, nasopharyngeal, and esophageal) determined average core temperature. RESULTS: All patients achieved a core target temperature of 42.5 degrees C for 2 hours. Electrolyte balance was maintained throughout hyperthermia (mean) in mmol/L: Na+, 136.2+/-2.2 mmol/L; K+, 4.0+/-0.3 mmol/L; Ca2+, 4.1+/-0.2 mg/dL; Mg2+, 1.9+/-0.1 mg/dL; PO4-, 4.5+/-0.9 mg/dL). Plasma cytokine concentration revealed significant heat-induced activation of proinflammatory and antiinflammatory cascades. All patients exhibited systemic vasodilation requiring norepinephrine infusion, 4 of 5 patients required vigorous diuresis, and 3 of 5 required intubation for 24 to 36 hours because of pulmonary edema or somnolence, with full recovery. Average length of hospital stay was 5.4 days. Serial tumor measurements (1 patient withdrew) revealed a decrease (64.5%+/-18%) in tumor size in 2 patients, no change in 1, and enlargement in 1, with no 30-day mortality. Median survival after hyperthermia treatment was 172 days (range, 40 to 271 days). CONCLUSIONS: Venovenous perfusion-induced systemic hyperthermia is feasible and provides the following potential advantages for better tumoricidal effect: (1) homogeneous heating, and (2) a higher sustained temperature.

Adult↗
PubMed2001

Quantitative assessment of a circulating depolarizing factor in shock.

Sustained depolarization of cell membranes and cellular edema are known to accompany various forms of circulatory shock and probably contribute to hypovolemia and cellular dysfunction. It has been proposed that a circulating protein is responsible for these effects. In the present study we have confirmed the existence of a circulating depolarizing factor (CDF) in hemorrhagic shock, burn shock, sepsis, and cardiopulmonary bypass. Plasma samples from pigs or sheep in shock were quantitatively assayed for depolarizing activity using a microelectrode method on rat diaphragm in vitro. The depolarizing effect of CDF in vitro was similar in magnitude to that of shock in situ. We conclude that CDF can entirely account for membrane depolarization during shock. The depolarizing effect of CDF was dose-dependent and saturable; it could be reversed by rinsing the diaphragm with Ringer's or control plasma. CDF activity was detectable in plasma within 5 min after a severe scald and gradually increased over the next 25 min. Resuscitation of hemorrhaged pigs, but not burned sheep, eliminated plasma CDF activity.

Animals↗
PubMed2001

Veno-venous perfusion-induced systemic hyperthermia: case report with perfusion considerations.

Cancer cells are more susceptible to destruction by heat than are their normal counterparts. However, optimization of this hyperthermic susceptibility for selective cancer cell kill has been difficult to define and technically difficult to achieve. A whole-body hyperthermic technique veno-venous perfusion-induced systemic hyperthermia (VV-PISH) was designed in in vitro and in swine experiments to achieve selective hyperthermic cancer cell destruction. In this case report, VV-PISH is studied for its safety and therapeutic efficiency in a Food and Drug Administration (FDA) approved phase-I study, where hyperthermia is used to treat advanced (Stage III B or IV) lung cancer. VV-PISH, utilizing the ThermoChem HT system in an extracorporeal circuit, was used to induce hyperthermia to 42.5 degrees C sustained for 120 min. Cooling returned the body temperature to 37 degrees C. After completion of the treatment, the patient was transferred to the intensive care unit on a ventilator, norepinephrine and diuretics. The patient remained somnolent for 36 h, developed pulmonary congestion requiring an additional 48 h before extubation, was transferred to the intermediate unit on day 4 and discharged in good condition on day 8. He did experience hyperthermia-related shrinkage of his lung cancer; however, he succumbed 270 days after this treatment from further progression of this disease. Hyperthermia is not a benign therapy; management techniques have been developed that have ameliorated many of the problems associated with extremely high temperatures, but pathophysiology still exists. Using these techniques, VV-PISH can be safety implemented, albeit not without temporary sequelae and further hospitalization.

Body Temperature↗
PubMed2000

Venovenous perfusion-induced systemic hyperthermia: hemodynamics, blood flow, and thermal gradients.

BACKGROUND: Thermal events during extracorporeal venovenous perfusion-induced systemic hyperthermia (VV-PISH) were studied and related to determination of whole-body and regional thermal isoeffect doses. METHODS: Swine (n = 6, 77+/-4.5 kg) were heated to a target temperature of 43 degrees C for 120 minutes using VV-PISH. Colored microspheres were injected during preheat, heat induction, maintenance, cool down, and after decannulation. The esophageal, tympanic, rectal, pulmonary artery, bladder, bone marrow, kidney, brain, blood, lung, and airway temperatures were recorded continuously. The thermal dose, thermal exchange, metabolic heat production, heat loss to the environment, the change in body heat, and the thermal isoeffect dose were studied at 15-minute intervals. RESULTS: VV-PISH increased heart rate and cardiac output and caused a redistribution of blood flow favoring the thoracoabdominal organs. Greatest thermal exchange occurred during the heating phase (total 2,162+/-143 kJ), metabolic heat production contributed in all phases (274+/-9 kJ), the greatest change in body heat occurred during heating (1,310+/-309 kJ) with a total delivered thermal dose of 298+/-21 kJ, and the total whole body thermal isoeffect dose at 100+/-5 minutes. CONCLUSIONS: VV-PISH is feasible, is capable of transferring sufficient heat, causes a redistribution of blood flow favoring the thoracoabdominal organs, and facilitates calculation of whole-body and regional thermal isoeffect doses.

Animals↗
PubMed2000

Oncogenic ras results in increased cell kill due to defective thermoprotection in lung cancer cells.

BACKGROUND: The survival response of normal cells to heat stress is an upregulation of heat shock proteins and ras protein activation. We hypothesized that in lung cancer cells the presence of oncogenic ras interferes with thermoprotective mechanisms resulting in cell death. METHODS: An equal number of lung tissue culture cells (normal and cancerous) were subjected to either heat stress and then recovery (43 degrees C for 180 minutes, 37 degrees C for 180 minutes) or recovery alone (37 degrees C for 360 minutes). End points were surviving number of cells, cell-death time course, heat shock protein (HSP70, HSC70, HSP27) expression before and after heat stress, and time course for HSP70 expression during heat stress and recovery. Heated cells were compared with unheated control cells, then this difference was compared between cell types. RESULTS: Heat stress in normal cells caused an 8% decrease in cell number versus a 78% +/- 5% decrease in cancer cells (p < 0.05). In normal cells, heat stress caused a 4.4-fold increase in HSP70, no change in HSC70, and a 1.7-fold increase in HSP27. In contrast, cancer cells initially contained significantly less HSP70 (p < 0.05), and there was a 27-fold increase in HSP70 and a 2-fold increase in HSC70 with no HSP27 detected (comparison significant, p < 0.05). HSP70 time course in normal cells showed that HSP70 increased 100-fold, reaching a vertex at 2 hours and remaining elevated for 24 hours; in cancer cells, HSP70 maximum expression (100-fold) peaked at 5 hours,,then decreased to slightly elevated at 24 hours. CONCLUSIONS: Cancer cells with oncogenic ras have defective thermoprotective mechanism(s) causing increased in vitro cell death, which provides an opportunity for thermal treatment of lung cancer.

Cell Count↗
PubMed2000

Technique of controlled reperfusion of the transplanted lung in humans.

BACKGROUND: Reperfusion injury remains a significant and sometimes fatal problem in clinical lung transplantation. Controlled reperfusion of the transplanted lung using white cell-filtered, nutrient-enriched blood has been shown recently to significantly ameliorate reperfusion damage in a porcine model. We modified this experimental technique and applied it to human lung transplantation. METHODS: Approximately 1,500 mL of arterial blood was slowly collected in a cardiotomy reservoir during the lung implant, and mixed to make a 4:1 solution of blood:modified Buckberg perfusate. This solution was passed through a leukocyte filter and into the transplant pulmonary artery for 10 minutes, at a controlled rate (200 mL/min) and pressure (less than 20 mm Hg), immediately before removal of the vascular clamp. RESULTS: Five patients underwent lung transplantation (1 bilateral, 4 single lung) using this technique. All patients were ventilated on a 40% fraction of inspired oxygen within a few hours and extubated on or before the first postoperative day. CONCLUSIONS: Controlled reperfusion of the transplanted lung with white cell-filtered, nutrient-enriched blood has given excellent functional results in our small initial clinical series.

Humans↗
PubMed1998

Acute normovolemic red cell exchange for cardiopulmonary bypass in sickle cell disease.

A patient with sickle cell disease (hematocrit, 28.5%; hemoglobin S fraction, 79%), required mitral valve repair. Partial red cell removal and blood component sequestration with an autotransfusion device before cardiopulmonary bypass initially decreased the sickle red cell mass. This was followed by an acute one-volume whole blood exchange transfusion performed upon the initiation of cardiopulmonary bypass, resulting in a further reduction. Both techniques yielded fresh autologous plasma for use; sequestration yielded a platelet-pheresis product. Adequate postbypass hemostasis was demonstrated.

Adolescent↗
PubMed1998

Extracorporeal heparin adsorption following cardiopulmonary bypass with a heparin removal device--an alternative to protamine.

OBJECTIVES: To evaluate the therapeutic efficacy and applicability of a heparin removal device (HRD) based on plasma separation and poly-L-lysine (PLL) affinity adsorption as an alternative to protamine in reversing systemic heparinization following cardiopulmonary bypass (CPB). DESIGN: A prospective study. SETTING: University research laboratory. SUBJECTS: Adult female swine (n=7). INTERVENTIONS: Female Yorkshire swine (n=7, 67.3+/-3.5 [SEM] kg) were subjected to 60 mins 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 which was connected to an HRD via extracorporeal circulation. Blood flow was drained at 1431.2+/-25.4 mL/min from the inferior vena cava, through the plasma separation chamber of the HRD (where heparin was bound to PLL), and reinfused into the right atrium. The HRD run time was determined by a previously established mathematical model of first-order exponential depletion. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, kaolin and celite activated clotting time (ACT), activated partial thromboplastin time (APTT), heparin concentration, and plasma free hemoglobin were obtained before, during, and after the use of the HRD. Pre-CPB ACT was 167+/-89 secs (kaolin) and 99+/-7 secs (celite), and APTT was 34+/-5 secs. The HRD run time averaged 27.4 +/-1.5 mins targeted to remove 90% total body heparin. Use of the HRD was not associated with any adverse hemodynamic reactions or increases in plasma free hemoglobin. The heparin concentration immediately following CPB was 4.85+/-0.24 units/mL, with ACT >1000 secs and APTT >150 secs in all animals. During heparin removal, total body heparin content followed first-order exponential depletion kinetics. At the end of the HRD run, heparin concentration decreased to 0.51+/-0.09 units/mL, with kaolin ACT returning to 177+/-22 secs, celite ACT returning to 179+/-17 secs, and APTT returning to 27+/-3 secs (p > .05 vs. pre-CPB baseline for all variables). CONCLUSIONS: The HRD is capable of reversal of anticoagulation following CPB without significant blood cell damage or changes in hemodynamics. The HRD, therefore, can serve as an alternative to achieve heparin clearance in clinical situations where use of protamine may be contraindicated.

Adsorption↗
PubMed1996

Adverse effects of postoperative infusion of shed mediastinal blood.

BACKGROUND: Postoperative infusion of shed mediastinal blood has been used in an effort to decrease blood usage after cardiac operations. Recent experience has suggested that this practice may actually lead to a delayed increase in bleeding. METHODS: In a prospective, randomized study, 40 patients undergoing coronary artery bypass grafting with shed mediastinal blood collected in a cardiotomy reservoir were divided into two equal groups and studied during their first 4 hours in the intensive care unit. Shed mediastinal blood was directly infused in group I (n = 20), whereas in group II (n = 20), it was not. In group II, if a sufficient volume of red cells was present to allow processing (n = 5), washed red cells were infused. Variables studied before and after infusion were the amount of blood lost and infused, homologous blood transfused, complete blood count and differential, serum fibrinogen, fibrin split products, D-dimers, clotting factors, prothrombin time, activated partial thromboplastin time, thromboelastograms, plasma-free hemoglobin, complement factors C3 and C4, creatine kinase and its MB isoenzyme, and body temperature. RESULTS: After infusion of shed mediastinal blood, elevated levels of fibrin split products and D-dimers were found in significantly more patients in group I. The thromboelastogram index was normal in 76% of patients in group II but in only 12.5% in group I. Group I also had an increase in band neutrophils, a greater number of febrile patients, higher serum levels of creatine kinase, its MB isoenzyme, and plasma-free hemoglobin, and greater blood loss during hours 3, 4, and 5 in the intensive care unit. The volume of red cells in shed mediastinal blood (hematocrit, 9% to 10%) was small, resulting in clinically insignificant autotransfusion when infused directly, and insufficient for cell processing in most patients. CONCLUSIONS: These data support those in previous studies that direct infusion of shed mediastinal blood does not save substantial amounts of autologous red cells and can cause a delayed coagulopathy and other adverse effects that may be harmful to patients postoperatively.

Adult↗
PubMed1996

Therapeutic hyperthermia.

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.

HIV Infections↗
PubMed1995

Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand.

Impaired gut mucosal perfusion has been reported during cardiopulmonary bypass. To better define the adequacy of gut blood flow and oxygenation during cardiopulmonary bypass, we measured overall gut blood flow and ileal mucosal flow and their relationship to mucosal pH, mesenteric oxygen delivery and oxygen consumption in immature pigs (n = 8). Normothermic, noncross-clamped, right atrium-to-aorta cardiopulmonary bypass was maintained at 100 ml/kg per minute for 120 minutes. Animals were instrumented with an ultrasonic Doppler flow probe on the superior mesenteric artery, a mucosal laser Doppler flow probe in the ileum, and pH tonometers in the stomach, ileum, and rectum. Radioactive microspheres were injected before and at 5, 60, and 120 minutes of cardiopulmonary bypass for tissue blood flow measurements. Overall gut blood flow significantly increased during cardiopulmonary bypass as evidenced by increases in superior mesenteric arterial flow to 134.1% +/- 8.0%, 137.1% +/- 7.5%, 130.3% +/- 11.2%, and 130.2% +/- 12.7% of baseline values at 30, 60, 90, and 120 minutes of bypass, respectively. Conversely, ileal mucosal blood flow significantly decreased to 53.6% +/- 6.4%, 49.5% +/- 6.8%, 58.9% +/- 11.6%, and 47.8% +/- 10.0% of baseline values, respectively. Blood flow measured with microspheres was significantly increased to proximal portions of the gut, duodenum and jejunum, during cardiopulmonary bypass, whereas blood flow to distal portions, ileum and colon, was unchanged. Gut mucosal pH decreased progressively during cardiopulmonary bypass and paralleled the decrease in ileal mucosal blood flow. Mesenteric oxygen delivery decreased significantly from 67.0 +/- 10.0 ml/min per square meter at baseline to 42.4 +/- 4.6, 44.9 +/- 3.5, 46.0 +/- 3.6, and 42.9 +/- 3.9 ml/min per square meter at 30, 60, 90, and 120 minutes of bypass. Despite the decrease in mesenteric oxygen delivery, mesenteric oxygen consumption increased progressively from 10.8 +/- 1.4 ml/min per square meter at baseline to 13.4 +/- 1.2, 15.9 +/- 1.2, 16.7 +/- 1.4, and 16.6 +/- 1.54 ml/min per square meter, respectively. We conclude that gut mucosal ischemia during normothermic cardiopulmonary bypass results from a combination of redistribution of blood flow away from mucosa and an increased oxygen demand.

Analysis of Variance↗
PubMed1995

Mixed venous oxygen saturation during cardiopulmonary bypass poorly predicts regional venous saturation.

Mixed venous oxygen saturation is generally accepted as an indicator of adequacy of systemic oxygen delivery; however, cardiopulmonary bypass (CPB) may alter this relationship. Major postoperative complications potentially secondary to inadequate oxygen delivery during CPB indicate that mixed venous oxygen saturation may not detect regional venous desaturation during CPB. We therefore tested the hypothesis that mixed venous oxygen saturation and pH did not predict regional venous oxygen saturations and pH during 2 h of bypass in a swine model. Six immature swine (27-34 kg) received standard normothermic CPB. Sagittal sinus and portal vein oxygen saturations and blood gases were measured at 30, 60, 90, and 120 min of bypass. Although the venous reservoir oxygen saturation remained unchanged during 2 h of bypass, sagittal sinus saturation and pH decreased significantly (66% +/- 3.3% to 33% +/- 2.2% and 7.38 +/- 0.04 to 7.23 +/- 0.05, respectively). Likewise in the portal vein, oxygen saturation and pH also decreased (82% +/- 2.4% to 59.3% +/- 3.9% and 7.39 +/- 0.03 to 7.27 +/- 0.06, respectively). We conclude that profound regional venous desaturation and progressive regional acidemia may go undetected even when a standard pump flow rate of 100 mL.kg-1.min-1 is used and mixed venous oxygen saturation is normal.

Animals↗
PubMed1994

Hypertonic saline/dextran for cardiopulmonary bypass reduces gut tissue water but does not improve mucosal perfusion.

Gut mucosal ischemia has been associated with cardiopulmonary bypass (CPB) and may contribute to postoperative systemic inflammatory response and multiorgan dysfunction. Hypertonic saline/dextran (HSD) has been previously shown to selectively increase mucosal blood flow in circulatory shock. To determine whether adding HSD to the prime solution for CPB improves gut mucosal blood flow and oxygenation, we performed normothermic, non-cross-clamped CPB in pigs with 1 ml/kg of HSD (25% NaCl/24% dextran 70) (HSD group, n = 9) or lactated Ringer's solution (LRS group, n = 9) as control added to a standard prime. Animals were instrumented with ultrasonic flow probes on the superior mesenteric artery (SMA), laser Doppler mucosal flow probes in the ileum, and indwelling portal vein catheters and tonometers for mucosal hydrogen ion measurements and pH calculations in the stomach, ileum, and rectum. The total infused volume and net fluid balance was significantly lower in the HSD than in the LRS group (649 +/- 171 ml vs 2075 +/- 385 ml and 502 +/- 182 ml vs 1891 +/- 363 ml, respectively, P < 0.01). SMA flow in the LRS group increased to 110-123% of baseline during CPB and was significantly higher than that in the HSD group which remained unchanged. Ileal mucosal blood flow decreased significantly to 70-50% of baseline in both groups with no difference between groups. Gut oxygen (O2) delivery decreased during CPB in both groups, but O2 consumption remained unchanged. Gastric, ileal, and rectal mucosal pH decreased progressively, and portal venous blood pH also decreased in both groups, but there was no significant difference between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Determination and comparison of heat exchange efficiency of four commercially available blood cardioplegia sets.

An in vitro comparison of the heat exchange properties of the Electromedics D1081A, Sarns MP-4 'Conducer Coil' 165720, Bentley HE-100 and the Shiley BCD Plus 4: 1 blood cardioplegia sets was performed. The efficiency was calculated for each heat exchanger and post-heat exchange blood path temperatures were compared. The calculated efficiency for each heat exchanger is as follows: Electromedics D1081A at 18 l/minute coil water flow (0.95); Sarns MP-4 165720 at 9 l/minute coil water flow (0.93); Bentley HE-100 at 10 l/minute coil water flow (0.91); Shiley BCD Plus at 15 l/minute coil water flow (0.90). Blood path, precoil temperatures for each unit were compared statistically with no differences found (p > 0.05). Blood side, postcoil temperatures were then compared. The average postcoil blood path temperature of the Electromedics D1081A was 1.6 degrees +/- 0.1 degree C, of the Sarns MP-4 165720 it was 2.1 degrees +/- 0.1 degree C, of the Bentley HE-100 it was 2.7 degrees +/- 0.3 degree C, and the Shiley BCD Plus 3.0 degrees +/- 0.4 degree C. The results of this experiment indicate that the average postcoil temperature of the Electromedics D1081A was lower than the Sarns MP-4 165720 (p < 0.05) which was lower than that of the Bentley HE-100 (p < 0.05) and Shiley BCD Plus (p < 0.05). No statistical difference was found between the average postcoil temperature of the Bentley HE-100 and the Shiley BDC Plus.

Blood Physiological Phenomena↗
PubMed1992

Transfusion guidelines for cardiovascular surgery: lessons learned from operations in Jehovah's Witnesses.

Patients undergoing cardiovascular surgery are among the top users of homologous blood transfusion (HBT). Awareness of the risks of disease transmission and immune system modulation from HBT has prompted us to find alternatives such as autologous predonation (APD) and intraoperative autotransfusion (IAT). However, these latter options are not appropriate for all patients. We reviewed our experience with 59 Jehovah's Witness patients who underwent 63 elective cardiovascular procedures without either HBT or APD to determine the safety of operation without these modalities and to develop revised maximum surgical blood-ordering schedule guidelines for cardiovascular surgery. Estimated blood loss averaged 870 ml, but one third to one half of losses were replaced by IAT. IAT was not needed in lower extremity bypass operations in which the estimated blood loss was less than 150 ml. Three of 59 patients died (5.1%), but only one died of operative bleeding complications. We conclude that (1) elective cardiovascular operations can be done safely without the use of either HBT or APD, (2) HBT is not necessary in leg bypass procedures, and (3) maximum surgical blood-ordering schedule guidelines for HBT in major cardiovascular operations can be reduced to near zero by the use of intraoperative autotransfusion and acceptance of a postoperative hemoglobin nadir of 7.0 gm/dl.

Blood Loss, Surgical↗