The relationship between vascular expansion of the aorta and pulmonary artery and the genesis of the impedance cardiogram using the technique of sonomicrometry.

PRIMARY OBJECTIVE: This prospective animal study aims to evaluate the contribution of the pulmonary artery (PA) and aorta on the morphology of the impedance cardiogram using sonomicrometry. METHODS: Impedance electrodes were placed around the thorax, aorta and in the oesophagus of five dogs. Sonomicrometry crystals were mounted on the PA and aorta for tracking vascular distension while a Doppler flow probe measured aortic blood flow. RESULTS: No significant differences (p > 0.05) were recorded between the onset of aortic expansion, aortic blood flow and the start of the impedance dZ/dt signal. Significant differences (p > 0.001) were recorded between the onset of PA expansion and the dZ/dt signal. PA expansion began 41.6 +/- 6.0 ms, 60.7 +/- 7.2 ms and 42.2 +/- 4.9 ms respectively, before surface, aortic and oesophageal impedance recordings. CONCLUSION: The genesis of the impedance cardiogram is attributed to volumetric expansion of the aorta.

A double-blind study to evaluate the safety of recombinant human hemoglobin in surgical patients during general anesthesia.

OBJECTIVE: To evaluate recombinant human hemoglobin (rHb1.1) in patients undergoing surgery involving general anesthesia; examine rHb1.1 for toxicity, including renal dysfunction and hypertension; and measure plasma concentrations of rHb1.1 over time. DESIGN: Prospective, double-blinded, randomized, placebo-controlled study. SETTING: University medical center hospital. PARTICIPANTS: Eighteen patients having surgery under general anesthesia. INTERVENTIONS: One of 4 escalating doses of rHb1.1 or normal saline (control) was administered by continuous infusion to patients receiving general anesthesia for elective surgical procedures. Total rHb1.1 doses ranged from 4.7 to 25.6 g. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory data, including vital signs monitoring, hematology (white blood cell and reticulocyte count, hemoglobin, hematocrit, erythrocyte sedimentation rates, and coagulation values), renal function (serum creatinine and blood urea nitrogen), hepatic function (mean and indirect bilirubin), pancreatic function (serum amylase and lipase), and antibodies (IgG and IgM) to Escherichia coli protein, were collected at specified intervals for 7 days after infusion of rHb1.1. No serious adverse events occurred. The most frequently observed clinical event occurred during the first 24 hours after infusion and was primarily associated with surgery and anesthetic administration. A slightly higher incidence of hypertension, symptoms suggestive of pyrogenicity, mildly elevated total and indirect bilirubin, and elevated pancreatic enzymes was observed in rHb1.1 treatment groups when compared with control. Hypertension resolved within 7 hours, and laboratory values returned to normal levels by day 7. CONCLUSION: Although the elevations in pancreatic enzymes seen in some rHb1.1-treated patients remain unexplained, the safety profile of rHb1.1 appears to be acceptable. These results support the continued clinical evaluation and development of rHb1.1.

Excitatory amino acid receptor antagonist 2APH may improve local CBF during cerebral ischemia in cats.

BACKGROUND: The present study was designed to investigate in a focal cerebral ischemia model the influence of 2APH, a competitive NMDA receptor antagonist, on the cerebral blood flow of cat cortex, given intravenously before cerebral ischemia. METHODS: Thirty-four male cats weighing 2.5 to 3.5 kg were anesthetized with halothane and then randomly assigned to either control or experimental group. In the experimented group 18 cats were treated with 2APH and in the control group 16 cats were given saline 10 min before middle cerebral artery occlusion (MCAO). Cortical blood flow (CBF), determined by laser Doppler ultrasound flowmetry, was measured 1 h, 2 h, 3 h, 4 h and 5 h after occlusion. Infarct volume was calculated by summing up the areas in each stained brain section after the experiment. RESULTS: There was a significant difference in the infarct volume of cortex between the 2APH group and the saline control group (P < 0.05). Moreover, we did notice an apparent decrease of the infarct volume in basal ganglia area when 2APH was given (P < 0.01). The total infarct volume was significantly smaller in the group treated with 2APH after MCAO as compared with the saline control group (P < 0.01). CONCLUSIONS: The data from the present experiment suggest that NMDA antagonists may not only antagonize the neurotoxic effect of excitatory amino acid on ischemic neuron but also improve the CBF of ischemic brain.

Administration of sevoflurane and isoflurane prior to prolonged global ischemia improves heart function in isolated rat heart.

BACKGROUND: The Langendorff model was used to determine whether pretreatment with sevoflurane, isoflurane, or ischemic preconditioning (IP) could protect the myocardium of rats against global ischemia. METHODS: After 15-min perfusion, each isolated heart was assigned to (1) CONTROL GROUP: no pretreatment, (2) Sevoflurane group: 20-min exposure of 1.7% sevoflurane prior to ischemia, (3) Isoflurane group: exposure of 1.4% isoflurane prior to ischemia, or (4) IP group: two 5-min ischemic periods separated by 5-min perfusion. Following pretreatment, each heart was exposed to 20-min global normothermic ischemia followed by 60-min reperfusion. Heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), HR x LVDP, left ventricular contractility (+dLVP/dt), and coronary flow were recorded continuously. Myocardial damage was assessed by hematoxylin and eosin (H&E) staining. RESULTS: No significant differences (P > 0.05) in hemodynamic variables were recorded among the four groups before the experiment. After ischemia during reperfusion, sevoflurane, isoflurane and IP pretreated hearts recovered left ventricular function significantly better than control hearts. After 60-min reperfusion, +dLVP/dt recovered to 6.84 +/- 1.06%, 23.3 +/- 4.80%, 42.3 +/- 3.16%, and 59.6 +/- 5.75% of baseline values respectively for control, sevoflurane, isoflurane and IP groups. HR x LVDP recovered to 8.9 +/- 1.7%, 27.9 +/- 6.42%, 38.7 +/- 2.78%, and 59.6 +/- 3.98% respectively. H&E staining supported the hemodynamic data in that hearts pretreated with sevoflurane, isoflurane and IP showed significantly less ischemic damage when compared to control hearts. CONCLUSIONS: Our study shows pretreatment with sevoflurane or isoflurane provided moderate protection to the isolated heart against prolonged periods of global ischemia.

Gene therapy: a novel method for the treatment of myocardial ischemia and reperfusion injury--mini-review.

Myocardial ischemia and reperfusion injury (MI/R) represents important sequelae of clinical events. Historically, a number of approaches including, surgical intervention, pharmacological therapy and physical exercise regimes have been prescribed for the treatment of patients with cardiovascular disease. Recently, however, attention has focused upon more novel approaches using gene-based therapies to treat cardiovascular and MI/R. This mini-review will examine the role that heat shock proteins (HSP), in particular the HSP70 family, and the antiapoptotic protein Bcl-2 play in myocardial protection. Also examined in this review are several techniques including adenovirus and Japan-Liposomal method for delivering genes into the myocardium.

Radiation therapy for tracheobronchial amyloidosis.

A 67-year-old man presented with localized tracheobronchial amyloidosis involving the distal trachea and the right-sided airways. The disease caused right middle lobe collapse and threatened the right upper and lower lobes. A variety of bronchoscopic methods, including Nd:YAG laser resection, dilation, and stenting, were used as temporizing methods. External beam radiation therapy, considered because of disease progression, caused a measurable local response. Radiation therapy should be considered as a treatment option for localized tracheobronchial amyloidosis causing airway obstruction.

Effects of dobutamine, norepinephrine and epinephrine on intramucosal pH and hemodynamics of dogs during endotoxic shock.

This study assessed the effects of dobutamine (DOB), epinephrine (EPI) and norepinephrine (NE) on gastric tissue oxygenation indicated by gastric intramucosal pH (pHi) and hemodynamics in dogs subjected to endotoxic shock. Twenty-four dogs were assigned to four groups of 6 dogs each: endotoxin without catecholamine and endotoxin with DOB, or EPI or NE. Endotoxic shock was induced by intravenous injection of 3 mg/kg of E. coli over 1 min, with an additional 3 mg/kg over the next 2 hrs. Dogs were resuscitated with normal saline to maintain pulmonary capillary wedge pressure (PCWP) near baseline levels. Catecholamines were infused at 0.1, 0.4 and 1.6 micrograms/kg/min (EPI and NE) and 2.5, 5.0 and 10.0 micrograms/kg/min (DOB) for 30 min at each rate. After 2 hrs of endotoxemia, mean arterial pressure (MAP) and cardiac index (CI) and oxygenation delivery index (DO2I) for all dogs decreased by 46.5%, 43.9% and 15.1% respectively, while pHi decreased from 7.47 to 7.10. Endotoxemia increased blood lactate by 142%. Following fluid resuscitation, EPI (1.6 micrograms/kg/min) further increased lactate by 178% (1.22 to 3.4 mmol/L). No correlation was found between tonometry pHi and lactate (R2 = 0.003), pHi and pHa (R2 = 0.231), pHi and DO2I (R2 = 0.056) nor between intramucosal PCO2 and PaCO2 (R2 = 0.005). pHi did not reflect the improvements in cardiovascular hemodynamics observed following administration of catecholamines. NE improved MAP, CI and DO2I whereas DOB produced similar effects as NE but further reduced SVR. EPI produced similar effects as NE. DOB, NE and EPI further decreased pHi. EPI significantly (P < 0.05) increased blood lactate levels more than DOB and NE.

Effects of dobutamine, epinephrine and norepinephrine on the hemodynamics of dogs during hemorrhagic shock.

BACKGROUND: The present study examined how effective epinephrine (EPI), norepinephrine (NOR) and dobutamine (DOB) were for resuscitating dogs subjected to hemorrhagic shock (HS). METHODS: Dogs (n = 42) were randomly assigned to seven test groups: EPI, NOR and DOB infusion with and without HS, and HS dogs with no catecholamine. Following baseline measurements, the dogs were bled to a mean arterial blood pressure of 40 mmHg. After 3 h, the shed blood was reinfused. EPI and NOR (0.1, 0.4 and 1.6 micrograms/kg/min) and DOB (2.5, 5.0 and 10.0 micrograms/kg/min) were given and the dog allowed to stabilize for 30 min. Hemodynamic and blood gas data were obtained at 6 time points (control, shock, resuscitation and after catecholamine infusion). RESULTS: There was no significant difference in myocardial performance (dP/dt) between the respective shocked and unshocked groups after blood resuscitation. In dogs without catecholamine infusion, CO and SvO2 continued to decline whereas SVR increased. DOB (2.5 to 10.0 micrograms/kg/min) with and without shock improved CO, LV dP/dt, SVR and SvO2. EPI did not further improve CO or SvO2 at infusion rates above 0.1 microgram/kg/min (with and without shock). NOR did not improve SvO2 at any infusion rate (with and without shock) and did not improve CO until the infusion rate was at 0.4 microgram/kg/min (without shock). CONCLUSIONS: This study advocates the use of both volume replacement therapy and DOB for resuscitation of HS dogs.

Monitoring body-core temperature from the trachea: comparison between pulmonary artery, tympanic, esophageal, and rectal temperatures.

INTRODUCTION: We designed an endotracheal tube (ETT) for acquiring body-core temperature from the trachea. This ETT had two temperature sensors, one attached to the inside surface of the cuff, the other mounted on the ETT shaft underneath the cuff. The ETT was evaluated in vitro and in dogs to determine: 1) optimal position of temperature sensors and 2) the responsiveness, accuracy, and resistance to ventilatory artifacts. METHODS: In vitro. An artificial trachea assessed the response-time and accuracy of ETT temperature sensors to abrupt temperature changes and ventilatory flow-rates. In vivo. Body temperature in 5 dogs was lowered to approximately 26 degrees C then elevated toward 39 degrees C using a heat exchanger during carotid-jugular bypass. ETT temperature measurements were compared simultaneously with those from the artificial trachea (in vitro) or from the pulmonary artery, tympanic cavity, esophagus, and rectum of dogs using dry and humidified gas. RESULTS: Cuff temperature sensor responded quickly and accurately to temperature changes and was less prone than the tube sensor to ventilatory and humidity artifacts. During carotid-jugular bypass, in vivo tube and cuff mean temperatures averaged 1.4 degrees C and 0.36 degree C lower, respectively, than pulmonary artery temperatures. There were no statistical differences (P > 0.05) between cuff temperatures and those measured from the pulmonary artery, tympanic cavity, esophagus, and rectum. Heating and humidifying the inspiratory gas of dogs with a water-bath humidifer or heat moisture exchanger (HME) had minimal effects on the cuff temperature sensor. An in-line HME increased in vivo tube temperature from baseline values by 1.13 +/- 0.80 degree C, while cuff temperature increased by 0.21 +/- 0.24 degree C. CONCLUSION: The cuff of the ETT is a reliable site for measuring body-core temperature in intubated patients.

Dosimetry and treatment planning of complex electron arc therapy.

Electron arc therapy has been primarily utilized for treatment of the post-mastectomy chest wall. Its clinical usefulness and benefits have been proven. Casting procedures and blocking techniques have been discussed. We have successfully applied electron arc therapy to the treatment of the nasal cavity and associated nodal regions. When compared to the chest wall, the smaller radii and pronounced irregularity of the surface anatomy of the facial region presents multiple new dosimetric and treatment planning challenges. We will discuss these challenges, along with those encountered in the casting procedures and reproduction of patient characteristics required for the execution of this treatment. Many aspects of dosimetry were utilized in unique ways to produce the treatment plans, cast and bolus needed. Due to the insertion of bolus into the nostrils, a unique hollow bite block was constructed to allow patient respiration during treatment. Film dosimetry was used to verify computer predictions and to compare this electron arc treatment technique with alternative fixed electron beam techniques. The potential benefits and difficulties of this technique will be discussed.

Monitoring normal and aberrant electrocardiographic activity from an endotracheal tube: comparison of the surface, esophageal, and tracheal electrocardiograms.

INTRODUCTION: We designed an endotracheal (ET) tube with orthogonally spaced ECG cuff electrodes. This ET tube was evaluated in dogs and sheep to determine (1) whether ECGs recorded from our tube were sufficient to make accurate clinical decisions concerning heart rate and rhythm; and (2) whether metallic cuff electrodes in direct contact with the trachea could induce mucosal burn injury during episodes of defibrillation. METHODS: Using experimental animals, we obtained ECGs from their tracheae and compared our findings with ECGs obtained from surface and esophageal electrodes. The electrical activity of the heart was modified by increasing the depth of anesthesia, occluding the left coronary artery, and administering beta-adrenergic drugs. Before the dogs were euthanized, they were subjected to episodes of transthoracic and intrathoracic defibrillation at energy levels of 200 to 400 J. A postmortem pathological examination of the trachea was performed to determine the incidence of mucosal burn injury. RESULTS: Tracheal electrocardiography provided valid information on heart-rate monitoring and certain morphology profiles. The R-R, PR, QRS, and QT intervals measured from the trachea had a correlation of 1.0, 0.96, 0.83, and 0.98, respectively, when compared with the same intervals obtained from surface electrodes. Two tracheae subjected to intrathoracic defibrillation at > 300 J revealed evidence of minor burn injury. Some localized epithelium loss was displayed in all tracheae; we attributed this to tracheal intubation. CONCLUSION: Tracheal electrocardiography may be useful in trauma patients who require intubation where injury precludes placement of chest ECG electrodes.

Computed tomography treatment planning in IR-192 brachytherapy in the head and neck.

Brachytherapy dose prescription and treatment planning lag behind the state-of-the-art for external beam therapy. As altered fractionation of external beam therapy improves patient outcome in head and neck cancer, there will be an increased need to compare the two radiotherapy techniques. Currently, implant techniques and dose prescription documentation are not uniform, dose prescription to a target volume is subjective, and implant quality is poorly understood and not routinely assessed. All contribute to a lack of scientifically rigorous brachytherapy clinical trials. Studies designed to combine tumor imaging and dosimetry data are important in the evolution of brachytherapy treatment planning. Head and neck implants, which often require nonparallel, arching, or looping source carriers for all but small tumors in order to encompass the target volume adequately, were used to evaluate the clinical utility and feasibility of computed tomography as a treatment planning tool in brachytherapy. Following placement of plastic afterloading tubes under general anesthesia, orthogonal radiographs with dummy sources in the afterloading tubes are obtained as customary for source localization. With the patient in the same position, axial CT scans are obtained with the dummy seeds still in place for treatment planning. The implant physician, using data from the pre-treatment diagnostic CT scan, outlines target areas on sequential images creating a 3-dimensional target volume. By superimposing anatomic data with isodose curves one can objectively define implant parameters important in clinical trials analysis. These include minimum target absorbed dose, implant uniformity, and treatment to target volume ratio. The results of the first 10 patients are presented and implications of these data regarding the analysis of implant technique, implant quality, and implant optimization are discussed. The technique as performed is laborious but practicable in the clinical research setting of head and neck implant. Further research efforts should improve, simplify, and objectify brachytherapy and hasten the time when rigorous multi-institutional brachytherapy trials will be reality.

Comparison of tidal ventilation and high-frequency jet ventilation before and after cardiopulmonary bypass in dogs using two-dimensional transesophageal echocardiography.

This study compared the use of high-frequency jet ventilation (HFJV) and tidal ventilation (TV) in a group of dogs with induced global myocardial ischemia before and after cardiopulmonary bypass. Transesophageal echocardiography was used to determine whether HFJV with its lower airway pressures could improve cardiac performance. The surgical procedure was separated into four study periods: closed chest before bypass, open chest before bypass, open chest after bypass, and closed chest after bypass. During each of these study periods, the dogs were randomly ventilated with alternate periods of TV and HFJV to maintain the PaCO2 at 34.3 +/- 3.3 mm Hg (mean +/- SEM). Cardiac output, stroke volume, systemic mean blood pressure, left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular dP/dt, left ventricular stroke work, and expiratory volumetric flows were higher during HFJV, whereas airway pressures and pulmonary vascular resistance were lower. Increases in cardiac output and stroke volume during HFJV were due to a combination of improved left ventricular contractility indicated by increased LV dP/dt and increased left ventricular end-diastolic volume accompanying decreased airway pressures. These data indicate that HFJV with its lower airway pressure is associated with significantly less impairment of cardiovascular function than TV in dogs with induced global myocardial ischemia.

Carotid thrombosis following neck irradiation.

Therapeutic irradiation may accelerate atherosclerosis, increasing the risk of vascular stenosis or occlusion several to many years following radiation. However, intimal damage following irradiation may result earlier in thrombosis without stenosis. This report discusses three cases of carotid occlusion that occurred within 3 years of moderate dose irradiation. Angiographic studies showed that occlusion occurred in the absence of atherosclerotic stenosis. A review of the literature supports the conclusion that people who receive neck irradiation are at risk not only for the delayed development of diffuse atherosclerosis but also for thrombotic occlusion within months to several years. We suggest that patients who develop neurological symptoms or signs following neck irradiation, regardless of age, dose of radiation, or interval since radiation, should be evaluated for carotid or vertebral artery disease.

Definitive radiation therapy in bile duct carcinoma.

Between 1980 and 1985, 24 patients with primary adenocarcinoma of the bile duct were treated with various combinations of surgery, biliary intubation, external irradiation, and transcatheter brachytherapy. Seventy-five percent of tumors were in the proximal bile ducts. Ten patients received no or only palliative radiation, Group 1, whereas 14 patients received definitive courses of radiation (4 by external beam irradiation, 2 by transcatheter irradiation, and 8 by both modalities), Group 2. Survival in Group 1 and Group 2 was significantly different (p less than 0.005) with median survivals of 2.0 and 12.8 months, respectively. This result may be in part due to differences in treatment and in part due to selection bias because the series is small, uncontrolled, and retrospective. Median survival of the 8 patients treated with combined modalities was 13.2 months (range 7.4-30.3) with 4 patients alive 8.7 to 16.2 months, 3 without cholangiographic evidence of disease. Complications of therapy were common, including bacterial sepsis (58%), cholangitis (38%), gastrointestinal bleeding (46%), intra or extrahepatic abscesses (33%), and recurrent biliary obstruction (25%). Cholangitis, hemorrhage, abscesses, and ulcers appeared more frequently in definitively treated patients, whereas recurrent biliary obstruction was absent in this group and frequent in Group 1. Differences in complication rates between groups were not statistically significant. Early diagnosis and management usually reversed a downhill clinical course in patients with abscess and hemorrhage. Both surgical and percutaneous techniques of biliary decompression, the usual initial form of therapy in bile duct cancer, are associated with frequent and serious complications. Although many of our complications may have derived from biliary decompression, it is possible that definitive treatment may have increased the frequency of serious complications.

Computer-controlled anesthesia delivery system.

A prototype Computer-Controlled Anesthesia Delivery System (CCADS) has been developed. The CCADS uses proportional, integral, and derivative (PID) software algorithms to control the delivery of oxygen, anesthetic agent,and nitrous-oxide (N2O) via the computer feedback control of precision mass-flow controller devices. The CCADS was evaluated in a group of seven dogs during 4 hours of closed-circuit enflurane N2O anesthesia. Throughout the 4-hour monitoring period, the CCADS maintained the animals' inspired oxygen concentration (FIO2), end-tidal enflurane concentration, and breathing circuit volume to within +/- 0.20, +/- 0.10 volume %, and +/- 30 ml/min (+/- 1 SD), respectively, of the desired values. The interactive software allowed selective graphic display of the 10-breath averaged data parameters, or modification of FIO2, end-tidal enflurane concentration, and breathing circuit volume, whenever animal re-evaluation during an anesthesia procedure was necessary.

Candidate products of avian myeloblastosis virus oncogene region produced by in vitro translation of genomic RNA.

Avian myeloblastosis virus (AMV) genomic RNA was translated in vitro to identify the AMV transforming gene (myb) product(s). Full-length RNA yielded, in addition to the expected Pr76gag, a gag-related product of 92,000 daltons which did not appear to be a gag-oncogene fusion protein. Subgenomic AMV RNA in vitro translation, nonstructural products (specific for AMV) were of 54,000, 49,000 and 34,000 daltons. Based on their sizes and similar peptide maps for the smaller two proteins, it is proposed that they derive from the myb region of AMV.

Monitoring anesthetic vapor concentrations using a piezoelectric detector: evaluation of the Engstrom EMMA.

The Engstrom anesthetic gas analyzer (EMMA) was evaluated to determine the reproducibility, response time, gas interference, water vapor dependence, and sensitivity. The analyzer also was evaluated clinically in 20 children undergoing orthopedic surgery. Difference between the analyzer output and anesthetic gas standard (reproducibility) ranged from 0.013 +/- 0.008 vol % to 0.018 +/- 0.018 vol %. Response times decreased from 710 ms at 5 l X min-1 to 149 ms at 30 l X min-1. Nitrous oxide caused an offset of +0.11 +/- 0.007 vol %. Water vapor caused positive offsets of 0.25 +/- 0.044 vol %, 0.51 +/- 0.027 vol %, and 0.80 +/- 0.037 vol % at 25 degrees C, 30 degrees C, and 34 degrees C, respectively. The analyzer reproducibly measured dry gas concentrations, but compensation had to be made for water vapor when measuring wet gases. The analyzer's usefulness for end-tidal monitoring was questioned because of its slow response time and its sensitivity to water vapor.

Feedback control of enflurane delivery in dogs--inspired compared to end-tidal control.

A technique was studied for the rapid induction of anesthesia in a closed rebreathing circuit using feedback control of end-tidal enflurane concentration. This technique was compared to anesthetic induction using a constant inspired concentration. In one group of seven dogs, end-tidal enflurane concentration was maintained at 2.0%. Electronic feedback control automatically decreased the inspired concentration from a maximum of 3.7% to 2.1% during a 4-hr period. In the second group of seven dogs, the inspired enflurane concentration was 2.0% throughout the study. There was no statistically significant difference between the two groups with regard to enflurane uptake, heart rate, blood pressure, or cardiac output. Enflurane uptake was higher in the first group only during the first 6 min after induction. The induction technique that used feedback control to automatically adjust the inspired enflurane concentration appeared to have no adverse cardiovascular effects beyond those present during an induction using a constant inspired concentration.