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Biomedical subjects

A DeAnda

Publications and source records attributed to A DeAnda.

33 records · Page 2Linked to original sources

Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass.

Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Left atrial pressure-clamp servomechanism demonstrates LV suction in canine hearts with normal mitral valves.

A novel technique is presented to study suction of the in situ left ventricle in open-chest experimental animals without requiring cardiopulmonary bypass or disturbing the native mitral valvular apparatus. In 17 dogs, left ventricular pressure (LVP) and left atrial pressure (LAP) were measured, the left atrium was cannulated and connected to a servo pump, and LAP was controlled to a setpoint near 0 mmHg by withdrawing blood from the left atrium. Heart rate [103 +/- 17 (SD) min-1], peak pressure (100 +/- 13 mmHg), minimum pressure (1.4 +/- 0.8 mmHg), and maximum rate of change of pressure with respect to time during isovolumic contraction and relaxation (2,506 +/- 775 and -1,761 +/- 855 mmHg/s, respectively) were normal. Servo control of LAP was possible to +/- 1 mmHg. LV suction was demonstrated in each heart (mean negative LVP -2.3 +/- 1.1 mmHg; P < 0.0001). This new technique demonstrates that the left ventricle can generate negative diastolic suction pressures when examined in vivo and in situ with an undisturbed mitral valve and physiologically normal preload and afterload. This adds to a growing body of evidence that, under appropriate circumstances, the heart can suck blood into itself and thereby aid in its own filling.

Animals↗

Coronary bypass grafting with biological grafts in a canine model.

BACKGROUND: Poor patency rates have limited the success of biological vascular grafts in the coronary artery position. Recently, two bovine internal mammary arterial grafts have been developed for possible use as coronary artery bypass graft (CABG) conduits: (1) Denaflex grafts (Baxter Health-care Co, 3-mm ID) treated with polyepoxy compounds and with heparin ionically bound to the luminal surface and (2) Bioflow grafts (Bio-Vascular, Inc, 3-mm ID) treated with dialdehyde starch. METHODS AND RESULTS: Thirty dogs underwent CABG with either a Denaflex (n = 20) or Bioflow (n = 10) graft to the left circumflex coronary artery (LCx). The left main coronary artery (n = 12) or proximal LCx (n = 18) was then ligated. Six-month patency (Kaplan-Meier) for Denaflex grafts was 44 +/- 13% (+/- SEM), compared with 12 +/- 11% for Bioflow grafts, but this difference did not reach statistical significance (P = .56). Among grafts open at 14 days, however, there were no occlusions among six Denaflex grafts versus five occlusions among seven Bioflow grafts. At 6 months, all six surviving Denaflex grafts appeared normal, while the only remaining patent Bioflow graft was angiographically dilated and had diffuse luminal irregularities. At 1 year, three Denaflex grafts angiographically had no dilation, stenosis, or luminal irregularities. Macroscopically, all explanted long-term (6 to 12 months) Denaflex grafts had a smooth, clean luminal surface, whereas the only patent Bioflow graft had multifocal thrombi. Microscopically, all Denaflex grafts had minimal degenerative changes, but the Bioflow graft had transmural linear cracks and medial deterioration. CONCLUSIONS: These data suggest that long-term (> 6-month) patency is possible with small-caliber, low-flow biological grafts in the canine coronary position, although both types of grafts are prone to early occlusion. If these early failures are excluded, the Denaflex graft appears to be associated with better long-term patency and an absence of degenerative changes.

Animals↗

Surgical management of aortic dissection in patients with the Marfan syndrome.

BACKGROUND: Aortic dissection is one of the most lethal potential complications in patients with the Marfan syndrome. METHODS AND RESULTS: Among 360 patients undergoing operative treatment of aortic dissection between 1963 and 1992, 40 had the Marfan syndrome. There were 24 men and 16 women with a mean age of 35 +/- 9 years (+/- 1 SD; range, 15 to 54 years). These patients included 16 with acute type A, 2 with acute type B, 18 with chronic type A, and 4 with chronic type B aortic dissections. The aortic arch was involved in 29 cases. Preoperative complications included acute aortic valvular insufficiency in 13 patients, rupture into the pericardial space in 3, and loss of peripheral pulses in 9. The site of primary intimal tear was the ascending aorta in 25 patients, the aortic arch in 2, the descending aorta in 7, and not identified in 6. Operations included ascending aortic and aortic valvular replacement (with or without coronary artery reimplantation) in 22 patients, ascending aortic replacement alone in 5, and descending thoracic aortic replacement in 9. Four operative deaths (10 +/- 5% [+/- 70% confidence limits]) occurred in 3 acute patient-years and 1 chronic type A patient-years. Long-term follow-up (216 patient-years; range, 1 month to 22 years; mean, 5.4 years) revealed 15 late deaths, 7 from late aortic sequelae. The overall actuarial survival estimates were 71 +/- 8%, 54 +/- 10%, and 22 +/- 11% at 5, 10, and 15 years, respectively. Twenty late aortic operations were required in 14 patients. CONCLUSIONS: Despite satisfactory early results, the long-term survival of patients with the Marfan syndrome was suboptimal (albeit similar to those without the Marfan syndrome). Future progress will pivot on reducing the incidence of aortic dissection in these patients with medical therapy and/or earlier surgical intervention and enhanced postoperative serial imaging surveillance of the entire aorta.

Actuarial Analysis↗

Left ventricular torsional dynamics immediately after mitral valve replacement.

BACKGROUND: Cardiac operations and cardiopulmonary bypass are associated with a host of unphysiological consequences that have widespread systemic effects. Since previous investigations in human cardiac transplant recipients had demonstrated that left ventricular (LV) torsional deformation was a sensitive method to detect subclinical LV dysfunction during acute rejection, we studied LV systolic torsion and diastolic recoil preoperatively and postoperatively in a canine model using myocardial marker techniques. METHODS AND RESULTS: Seven dogs underwent placement of LV subepicardial myocardial markers and creation of mitral regurgitation. Three months later, the animals underwent high-speed, biplane videofluoroscopic analysis for determination of LV systolic function and regional LV systolic torsional deformation and diastolic recoil. The animals then underwent chordal-sparing mitral valve replacement and were restudied 1 to 2 hours postoperatively. One to 2 hours after the cardiac operation, regional maximal systolic torsional deformation decreased significantly in all three LV regions on the lateral LV wall, as well as in the apical and apical-equatorial regions on the anterior wall. During early systole, minimal regional systolic torsion increased significantly in all regions on the lateral wall, as well as in the apical level of the posterior wall. Heterogeneous decreases in torsional deformation were also seen during the early diastolic filling period. CONCLUSIONS: Regional systolic torsional deformation and diastolic recoil are markedly perturbed early after a cardiac operation and its associated manipulations. Such changes, however, may potentially serve as sensitive tools to assess the impact of different techniques of intraoperative management, including newer methods of myocardial protection.

Animals↗

Effects of left ventricular support on right ventricular mechanics during experimental right ventricular ischemia.

BACKGROUND: Left ventricular (LV) assist device (LVAD) support has been associated with right ventricular (RV) failure in humans, but the etiology remains unknown. Mechanical LV support apparently does not induce RV pump failure in normal hearts, but controlled studies of LV assistance in hearts with preexistent RV dysfunction have been limited. Therefore, this study was performed to determine if LVAD support impairs RV systolic mechanics during acute RV ischemia. METHODS AND RESULTS: Five closed-chest, autonomically blocked, sedated dogs were studied after placement of an LVAD (LV-femoral artery bypass), right coronary artery (RCA) occluder, and 27 miniature radiopaque tantalum markers into the LV and RV walls for independent computation of RV and LV volumes. Biplane videofluoroscopic marker images and hemodynamic data were recorded before RCA occlusion with the LVAD off (maximum LV pressure [LVPmax] = 119 +/- 25 mm Hg), after 3 minutes of RCA occlusion with the LVAD off (LVPmax = 84 +/- 18 mm Hg), and then with the LVAD on (LVPmax = 26 +/- 32 mm Hg). Global RV contractility (end-systolic elastance [RV Ees] and preload recruitable stroke work [RV PRSW]), RV power output, and the mechanical (pump) efficiency of converting potential energy to external work (ratio of RV stroke work/total pressure-volume area) were calculated. As expected, with RCA occlusion there were major decreases in RV Ees (from 2.5 +/- 1.2 to 1.4 +/- 0.5 mm Hg/mL, P < .005) and RV PRSW (15 +/- 4 versus 9 +/- 4 mm Hg, P < .001). RV power output (overall pump performance) declined by 39 +/- 20% (P < .025), and mechanical efficiency fell by 38 +/- 13% (P < .001). After initiation of mechanical LV support, however, there was no further impairment of RV contractility or power output (P > .80). Pulmonary artery input impedance (RV afterload) decreased from 848 +/- 628 to 673 +/- 577 dyne.sec-1.cm-5 (P < .01), which led to a 26 +/- 29% improvement in RV pump efficiency (P < .001). CONCLUSIONS: While right coronary artery occlusion significantly reduced RV systolic performance, LVAD support during acute RV ischemia did not further impair RV contractility or power output. Furthermore, since RV afterload fell with LV unloading, the mechanical pump efficiency of the right ventricle actually improved. These observations demonstrate that LVAD support does not directly induce RV failure in canine hearts with acute isolated RV ischemia.

Animals↗

Right ventricular dynamics during left ventricular assistance in closed-chest dogs.

To determine the effects of left ventricular assist device (LVAD) support on global right ventricular (RV) systolic mechanics, 8 closed-chest, conscious, sedated dogs were studied after placement of an LVAD (left ventricle to femoral artery bypass) and implantation of 27 tantalum markers into the left ventricular and RV walls for computation of biventricular volumes and geometry. Biplane cinefluoroscopic marker images and hemodynamic parameters were recorded during transient vena caval occlusion at various levels of LVAD support. Right ventricular contractility was assessed using end-systolic elastance and preload recruitable stroke work, and the myocardial (pump) efficiency of converting mechanical energy to external work (stroke work/total pressure-volume area) was calculated. With full LVAD support, RV end-diastolic volume increased from 60 +/- 15 to 62 +/- 17 mL (p < 0.002), pulmonary artery input impedance decreased from 940 +/- 636 to 587 +/- 347 dyne.s/cm5 (p < 0.007), and measurement of RV and left ventricular septal-free wall dimensions demonstrated a significant leftward septal shift (p < 0.0005). Global RV end-systolic elastance and preload recruitable stroke work decreased from 2.4 +/- 1.0 to 1.7 +/- 0.7 mm Hg/mL (p < 0.004) and 14.1 +/- 3.3 to 12.1 +/- 3.9 mm Hg (p < 0.02), respectively; however, RV power output and myocardial efficiency did not change significantly (p > 0.74 and p > 0.33, respectively). Therefore, during LVAD support, global RV contractility is impaired with leftward septal shifting, but RV myocardial efficiency and power output are maintained through a decrease in RV afterload and an increase in RV preload.

Animals↗

Role of experience in the response to simulated critical incidents.

Eight experienced anesthesiologists (faculty or private practitioners) were presented with the same simulated critical incidents that had previously been presented to 19 anesthesia trainees. The detection and correction times for these incidents were measured, as was compliance with Advanced Cardiac Life Support (ACLS) guidelines during cardiac arrest, and the occurrence of unplanned incidents. Experienced personnel tended to react more rapidly than did trainees, but differences between second-year anesthesia residents (CA2) and experienced anesthesiologists were not statistically significant. There was a high variability in performance between incidents and within each group. Unplanned errors and management flaws still occurred with experience subjects. The response to incidents during anesthesia is a complex process that involves multiple levels of cognitive activity and is vulnerable to error regardless of experience. Most trainees seemed to acquire adequate response routines by the end of the CA2 year. Formal reasoning appeared to play a minor role in responding to intraoperative events, but the exact nature of the anesthesiologist's cognition remains to be thoroughly investigated.

Anesthesiology↗

Unplanned incidents during comprehensive anesthesia simulation.

In analyzing recordings of first- and second-year residents performing anesthesia in a comprehensive anesthesia simulation environment (CASE 1.2), we noted the occurrence of unplanned incidents. Utilizing a modified critical incident technique, we documented 132 unplanned incidents during 19 simulations (range 3-14, mean 6-947). Ninety-six (73%) of the incidents were considered simple incidents, and 36 (27%) were considered critical incidents. The incidents were classified as either human errors (65.9%), equipment failures (3%), fixation errors (20.5%), or unknown causes (10.6%). Human errors accounted for 87 of the incidents (range 1-12, mean 4.579), fixation errors accounted for 27 of the incidents (range 0-3, mean 1.421), and equipment failures accounted for only four of the incidents (range 0-2, mean 0.211). There was a significant (P less than 0.025) difference overall between resident groups, although no one class differed significantly from the others. The data confirm that most incidents are due to human error rather than equipment failure, and document fixation errors as a frequent cause of incidents in anesthesia. The data indicate that although most incidents are simple and do not progress into more serious incidents, human error remains ubiquitous, and that formal training and education should include recognition of events and the responses to them, in addition to prevention.

Anesthesiology↗

The response of anesthesia trainees to simulated critical incidents.

Using a comprehensive anesthesia simulation environment (CASE 1.2) we studied the response of anesthesia trainees (10 first-year residents and 9 second-year residents) to five simulated critical incidents: 1) endobronchial intubation; 2) kinked IV; 3) atrial fibrillation with hypotension; 4) breathing circuit disconnection; 5) cardiac arrest. Simulations were videotaped, and the response times for detecting and initiating correction of the problems were measured. Different problems had significantly different response characteristics. Breathing circuit disconnection and cardiac arrest were quickly detected (21 +/- 17 seconds; 7 +/- 5 seconds), and correction was begun quickly, although major errors in managing the cardiac arrest occurred in 58% of cases. Endobronchial intubation and atrial fibrillation took longer than the other problems to detect (105 +/- 142 seconds; 111 +/- 158 seconds) and to correct (555 +/- 358 seconds; 365 +/- 121 seconds). Intravenous kink was detected more slowly (238 +/- 269 seconds) but once discovered was quickly corrected. The response of different individuals was highly variable; experience level was a significant factor for correction (P = 0.03) but not for detection of problems overall. Because of high individual variation, experience was not a significant factor in correcting any signal problem. The data suggest that some types of problems are harder to handle than others and that individuals vary widely in their problem-handling abilities. Experience is a beneficial factor in anesthesia problem solving but not in a simple fashion. Vigilant detection of problems is only the first step in a complex response pathway that might be strengthened by improved protocols and repeated practice.

Anesthesia↗

Lactate extraction and myocardial damage after countershock at different energy levels.

The relationship between myocardial lactate metabolism and the energy dose of direct countershock was studied in 15 dogs anesthetized with halothane. Five dogs received two shocks of 5 joules delivered energy each, five animals received two shocks of 10 joules delivered energy each, and five dogs received two shocks of 20 joules delivered energy each. All animals had positive myocardial lactate extraction in the baseline state (5 joules, 38% +/- 23.7 (SD); 10 joules, 59.6% +/- 11.4; 20 joules, 38% +/- 11.1). Lactate extraction after countershock progressively decreased with increasing energy dose and then returned to baseline. The maximal reduction in percent lactate extraction increased with increasing energy dose (5 joules, 13.9% +/- 16.1; 10 joules, 33% +/- 37; 20 joules, 30.5% +/- 37.5) and seemed to reach a threshold below which no further decrease occurred. Myocardial damage, as measured by a damage index derived from myocardial uptake of technetium-99 pyrophosphate, increased steadily with increasing energy dose (2.0 +/- 2.5 with 5-joule shocks; 38 +/- 32 with 10 joules; and 99 +/- 70 with 20 joules). These results show a consistent reduction in aerobic metabolism immediately following electric countershock. Even at low-energy doses, myocardial lactate extraction showed a detectable decrease and at higher energies approached net lactate production. Reductions of global lactate extraction did not completely predict the amount of myocardial damage. Localized measures of anaerobic metabolism or mitochondrial function might provide a better correlation with localized damage.

Anesthetics, Inhalation↗

A comprehensive anesthesia simulation environment: re-creating the operating room for research and training.

Simulation is used extensively in industries that involve routine, but risky activities. The authors describe an anesthesia simulation environment that provides a re-creation of the anesthesiologist's task environment in a real operating room. The system provides appropriate inputs to standard monitoring equipment in common use during anesthesia, including ECG (with arrhythmias); invasive systemic arterial, pulmonary arterial, and central venous pressures (all coupled to ECG arrhythmias); automated cuff blood pressure; pulse oximetry; mass spectrometry; breathing circuit spirometry; and oxygen analysis. An intubation/thorax mannequin allows tracheal intubation and tube manipulation, and provides for simulation of occlusion, malposition, or disconnection of the tracheal tube, as well as regurgitation of gastric contents. The simulation is comprehensive in that it is "hands-on" and requires actual performance of most interventions using actual equipment. The simulation is conducted by a systems operator and a simulation director; the latter also acts in the roles of surgeon and circulating nurse. The simulator outputs are determined by a "script" that defines the consequences of routine anesthetic actions and pre-established critical incidents. Decisions about timing and override of the script are made by the simulation director. This control system offers maximum flexibility while maintaining clinical realism. The simulator experiences were judged as highly realistic by 21 subjects. Limitations in this version have centered on the mannequin (e.g., no patient movement, minimal or confusing physical signs) and will be addressed in future versions of the system. The authors suggest that anesthesia simulation can be accomplished at nominal expense and has major potential for training, continuing education, certification, and research.

Anesthesia↗

Anesthetic mishaps: breaking the chain of accident evolution.

Anesthesia and surgery are a risk for all, the healthy as well as the sick. While the prevention of adverse outcomes in healthy patients is paramount, enhancement of safety for critically ill patients is also essential, since they are more likely to suffer a SNO after a critical incident. Dangers originate from a variety of sources, not solely from errors by the anesthesiologist. Simple incidents of all description are inevitable, and we should focus on promoting recovery as well as avoiding error. Processes that lead to negative outcomes after critical incidents should be investigated to reduce the uncertainty complexity associated with managing the human body during anesthesia, and to establish the most effective detection and recovery techniques. Outcome studies are lacking, and clinical and animal research is highly dependent on the chosen model or population, making the results hard to apply to variable clinical conditions. Wherever possible, a consensus should be sought on therapeutic and adverse effects of drugs and techniques in common, specific patient populations. These can serve as a basis for developing therapeutic plans, recognizing that customizing to individuals is always necessary. A mainstay of anesthetic practice already involves attempts to loosen couplings, by keeping homeostatic mechanisms intact when possible (awake intubation, regional anesthesia); providing temporal buffers (titration of drugs, and use of drugs with short onset times and rapid termination of effect); and providing safety margins using appropriate pre-treatments (pre-oxygenation, atropine in children, etc.). Further means of loosening coupling should be identified and promoted. Specific attention to recovery from simple incidents should attack several facets of the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Accident Prevention↗

Pitfalls in creation of left atrial pressure-area relationships with automated border detection.

Creation of pressure-area relationships (loops) with automated border detection (ABD) involves correction for the variable inherent delay in the ABD signal relative to the pressure recording. This article summarizes (1) the results of in vitro experiments performed to define the range of, and factors that might influence, the ABD delay; (2) the difficulties encountered in evaluating a thin-walled structure like the left atrium in the dog model; and (3) the solutions to some of the difficulties found. The in vitro experiments showed that the ABD delay relative to high-fidelity pressure recordings ranges from 20 to 34 msec and 35 to 57 msec at echocardiographic frame rates of 60/sec and 33/sec, respectively. The delay was not influenced significantly by the type of transducer used, distance from the target area, or size of the target area. The delay in the ABD signal, relative to the echocardiographic image, ranges from nil to less than one frame duration, whereas it is delayed one to two frame durations relative to the electrocardiogram processed by the imaging system. In the dog model, inclusion of even small areas outside the left atrium rendered curves with apparent physiologic contour but inappropriately long delays of 90 to 130 msec. To exclude areas outside the left atrial cavity, time-gain compensation and lateral gain compensation were used much more extensively than during left ventricular ABD recording. By changing the type of sonomicrometers used in our experiments, we were able to record simultaneously ABD and ultrasonic crystal data. However, both spontaneous contrast originating from a right-sided heart bypass pump and electronic noise from the eletrocautery severely interferred with ABD recording.

Animals↗