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Biomedical subjects

P D Beckley

Publications and source records attributed to P D Beckley.

13 recordsLinked to original sources

Left ventricular myocardial adenosine triphosphate changes during reperfusion of ventricular fibrillation: the influence of flow and epinephrine.

OBJECTIVE: To determine whether epinephrine in combination with high flow worsens left ventricular (LV) myocardial high-energy phosphate stores during reperfusion of ischemic ventricular fibrillation (VF). DESIGN: Blinded, prospective block randomized, placebo controlled study. SETTING: University medical center research laboratory. SUBJECTS: A total of 22 mixed breed swine weighing 22.0+/-3.3 kg (SD). INTERVENTIONS: Open-chest swine, anesthetized with alpha-chloralose, underwent 10 mins of nonperfused VF followed by reperfusion with cardiopulmonary bypass for 90 mins and then defibrillation. Animals were block randomized to four groups for reperfusion: Group 1 (n = 5), high flow (100 mL/kg/min) and epinephrine (2.5 microg/kg/min); Group 2 (n = 5), high flow and placebo; Group 3 (n = 6), low flow (30 mL/kg/min) and epinephrine; and Group 4 (n = 6), low flow and placebo. MEASUREMENTS AND MAIN RESULTS: In vivo LV creatine phosphate (CP) and adenosine triphosphate (ATP) were determined using whole wall and spatially localized 31P NMR spectroscopy at 4.7 Tesla. During perfusion of the fibrillating myocardium, epinephrine significantly increased aortic pressure (p < .05) and improved defibrillation rates (p < .01). ATP levels during reperfusion were significantly decreased within all groups compared with baseline. There were no differences in ATP levels between groups. High flow, independent of epinephrine, was associated with increased preservation of ATP (p < .05), increased CP/ATP ratios (p < .02) in all layers of the LV wall, and decreased aortic and cardiac vein lactates (p < .001). CONCLUSIONS: Epinephrine, in combination with flow higher than standard cardiopulmonary resuscitation flows, increased perfusion pressure and defibrillation rates, but did not significantly alter myocardial ATP during VF reperfusion in the in vivo heart Reperfusion flow, independent of epinephrine, is a critical determinant of myocardial ATP preservation.

Adenosine Triphosphate↗

Flow requirements in ventricular fibrillation: An in vivo nuclear magnetic resonance analysis of the left ventricular high-energy phosphate pool.

STUDY OBJECTIVE: We sought to determine whether flow rates of approximately 60% of normal values are sufficient to preserve the left ventricular myocardial high-energy phosphate pool during ventricular fibrillation (VF). METHODS: Mixed-breed swine (weight 22. 4+/-2.5 kg) were anesthetized with alpha-chloralose, placed in a state of VF, and perfused with extracorporeal circulation at a target flow of 50 mL.kg(-1).min(-1). In vivo whole-wall (average of left ventricular wall) and spatially localized phosphorous-31 nuclear magnetic resonance (NMR) spectra were acquired at baseline and during VF. RESULTS: Mean flow during VF was 58+/-20 mL.kg(-1). min(-1) (+/-SD; 95% confidence interval, 44 to 71) or about 60% of baseline cardiac output (n=13). Whole-wall adenosine triphosphate (ATP) decreased during perfused VF (P <.05), whereas creatine phosphate (CP) remained unchanged from baseline. With spatially localized NMR, the ratios of CP/ATP were similar at baseline in all layers (endocardium --> epicardium) of the left ventricular wall. However, during perfused VF, subepicardial CP/ATP ratios increased by 14% to 40% compared with baseline values, whereas subendocardial CP/ATP ratios remained unchanged (1% to 3% increase). An additional 4 animals perfused at 72+/-10 mL.kg(-1).min(-1) (+/-SD; 95% confidence interval, 56 to 92) during VF had preservation of CP and ATP levels. CONCLUSION: Flow levels equivalent to 60% of baseline cardiac output were insufficient to maintain normal high-energy phosphate levels in the in vivo fibrillating myocardium. At this level of flow, myocardial high-energy phosphate loss is nonhomogeneous within the left ventricular wall.

Adenosine Triphosphate↗

In-vivo myocardial substrate alteration during perfused ventricular fibrillation.

OBJECTIVES: Earlier work suggests the in-vivo heart alters its substrate utilization as a function of cardiac work. Previous work has also demonstrated the high oxygen requirements of the heart during ventricular fibrillation (VF). The authors hypothesized that myocardial substrate utilization during VF with perfusion is similar to the normal beating heart under conditions of increased workload. METHODS: Myocardial substrate selection was studied in the in-vivo porcine myocardium using 13carbon nuclear magnetic resonance (13C NMR) under conditions of increased cardiac work (dobutamine group) and VF with extracorporeal perfusion (VF group). Once the animal preparation was completed, metabolic steady state was achieved with the infusion of unlabeled acetate into the left anterior descending (LAD) coronary artery. The infused substrate was then changed to [2-13C] acetate and glutamate pool labeling was monitored by 13C NMR. The glutamate C4 resonance areas at baseline and after intervention of either increased workload (dobutamine group) or perfused VF (VF group) were compared within groups using paired t-tests. RESULTS: Baseline aortic and great cardiac vein lactates, glucose levels, blood gases, hemoglobin levels, and temperatures were similar between groups. In both groups, there was a significant decrease from baseline in the labeling of C4 glutamate peaks (dobutamine group: 20.2+/-14.9 vs 84.7+/-32.7, p = 0.002; and VF group: 49.8+/-24.4 vs 83.9+/-24.4, p = 0.02), indicating selection against acetate oxidation in favor of other endogenous substrates. CONCLUSIONS: In the in-vivo heart, despite the absence of functional contractions, changes in substrate utilization during perfused VF are similar to changes that occur with increased workload in the normal beating heart.

Acetates↗

A comparison of gaseous emboli release in five membrane oxygenators.

The purpose of this study was to compare the air handling capability of five currently used membrane oxygenators: the Avecor Affinity, the Bentley SpiralGold, the Medtronic Maxima Plus, the Sarns Turbo and the Sorin Monolyth M. A circuit was constructed to include a hardshell venous reservoir and roller pump. Pressure monitoring sites and ultrasonic microbubble detection probes were located proximal and distal to the oxygenator. An air injection/infusion site was provided proximal to the roller pump inlet. Each circuit was primed with fresh anticoagulated bovine blood, adjusted to a haematocrit of 25% and maintained at 38 +/- 1 degree C. Three different bolus amounts of air (10, 20 and 40 cm3) were injected at three blood flow rates (3, 4.5 and 6 l/min). A 1-min infusion of air delivered at 1 ml/s was also administered at three blood flow rates (3, 4.5 and 6 l/min). The hardshell reservoir was also completely emptied at each flow rate to simulate a massive air infusion. At any given blood flow, outlet microbubble counts were usually higher with greater bolus amounts of air. When indexed to the inlet bubble counts, the following average percent microbubbles were released from the outlet: Turbo 25%, Affinity 7%, Monolyth 5%, Maxima 3% and SpiralGold 1%. With a constant air infusion of 1 ml/s, greater outlet microbubble counts were associated with higher blood flow rates. Again, when indexed to the inlet bubble counts, the following average percent microbubbles were released from the outlet: Turbo 44%, Affinity 25%, Maxima 19%, Monolyth 16% and SpiralGold 0%. All oxygenators deprimed when the hardshell reservoir was emptied and all shed microbubbles into the outlet blood except the SpiralGold. The results of this study indicate that air handling is not a simple function of blood flow pattern (i.e. top to bottom versus bottom to top), but also includes dynamics associated with oxygenator design, fibre arrangement and flow resistance.

Animals↗

Comparison of the performance characteristics of three generations of membrane oxygenators: Univoxregistered, Univoxreqistered Goldtrademark and SpiralGoldtrademark.

With continuous enhancement in oxygenator design, the question is raised as to how these changes actually impact the performance of the oxygenator. The recent addition of two new oxygenators by the Bentley Division of Baxter Healthcare Corporation provided us with a unique opportunity to compare the performance of each device and isolate the impact of each design change on performance. While the basic design and flow patterns have remained the same, application of the Duraflo II treatment has produced the Univox Gold and a change in the fibre-winding technique has produced the SpiralGold. This study compared the effects of heparin coating (Univox to Univox Gold) and fibre-winding (Univox Gold to SpiralGold) on gas and heat transfer and resistance to blood flow (pressure drop). Six oxygenators of each model were evaluated utilizing an in vitro single pass circuit, which first conditioned bovine blood to the Association for the Advancement of Medical Instrumentation (AAMI) venous standards. Blood flows of 4.0, 5.0, 6.0 and 7.0 l/min, FiO2 values of 1.0, 0.8 and 0.6, and gas-to-blood flow ratios of 0.5, 1.0 and 1.5 were chosen as test variables. Data generated included oxygen transfer, carbon dioxide transfer, arterial pO2, resistance to blood flow, and coefficient of heat exchange. The results indicate that the Duraflo II treatment does not have a significant effect on gas and heat transfer or resistance to blood flow. The fibre-winding technique employed with the new SpiralGold, however, has improved significantly gas exchange and arterial pO2 when compared with the previous Univox models. Resistance to blood flow and coefficient of heat exchange were not affected significantly by the winding technique.

Carbon Dioxide↗

Myocardial metabolic changes during reperfusion of ventricular fibrillation: a 31P nuclear magnetic resonance study in swine.

OBJECTIVE: Myocardial metabolic requirements during reperfusion of ventricular fibrillation are poorly understood. The objective of this study was to determine if controlled reperfusion after a clinically relevant global ischemia period of 10 mins was sufficient to prevent or reverse myocardial ischemia as indicated by changes in myocardial high energy phosphates, myocardial intracellular pH, and great cardiac vein lactate. DESIGN: Prospective laboratory study with controlled reperfusion. SETTING: Research laboratory at a university medical center. SUBJECTS: Five swine weighing 19 +/- 3 kg. INTERVENTIONS: Ten minutes of nonperfused ventricular fibrillation followed by reperfusion with cardiopulmonary bypass (flow 30 mL/kg/min) for 50 mins. MEASUREMENTS AND MAIN RESULTS: Myocardial adenosine triphosphate (ATP), phosphocreatine, and intracellular pH were determined using in vivo 31P nuclear magnetic resonance. Myocardial blood flow, measured by 15-mu radiolabeled microspheres, was significantly increased above baseline during reperfusion. Phosphocreatine was depleted during the 10 mins of nonperfused ventricular fibrillation, but recovered to 122 +/- 18% of baseline with reperfusion and was 112 +/- 18% at 60 mins (p < .005). ATP concentrations decreased to 51 +/- 16% of baseline after 10 mins of nonperfused ventricular fibrillation, improved to 67 +/- 9% of baseline with early reperfusion, and were 65 +/- 9% of baseline at 60 mins (p < .02). Myocardial intracellular pH improved from 6.11 +/- 0.18 after 10 mins of nonperfused ventricular fibrillation, to 6.89 +/- 0.20 with early reperfusion, and then decreased to 6.85 +/- 0.35 at 60 mins ventricular fibrillation (p < .001). Despite myocardial blood flows higher than baseline during the reperfusion period, great cardiac vein/aortic lactate gradient increased over the reperfusion period. CONCLUSION: Prolonged reperfusion with supranormal myocardial blood flow does not restore normal myocardial aerobic metabolism in the fibrillating myocardium after a 10-min nonperfused ventricular fibrillation period.

Adenosine Triphosphate↗

Organ blood flow following cardiac arrest in a swine low-flow cardiopulmonary bypass model.

STUDY OBJECTIVE: To determine organ blood flow changes, relative to baseline, following cardiac arrest and resuscitation in a closed-chest cardiac arrest swine model using cardiopulmonary bypass to achieve reproducible return of spontaneous circulation (ROSC). INTERVENTIONS: Following 10 min of ventricular fibrillation (VF), animals (n = 10) received low-flow cardiopulmonary bypass at 10 ml/kg/min from 10-15 min. At 15 min of VF, norepinephrine (0.12 mg/kg) was given and bypass flow increased to 50 ml/kg/min, followed by countershocks at 16 min. Following ROSC, cardiopulmonary bypass was immediately weaned off with norepinephrine support. Organ blood flows were determined during normal sinus rhythm, during reperfusion of VF and during the early post-ROSC period while off cardiopulmonary bypass support. Organ blood flows during the early ROSC period were compared with organ blood flow at baseline and during VF. RESULTS: During early reperfusion of VF prior to any drug therapy, myocardial, cerebral and abdominal organ blood flows were all low. All animals achieved ROSC at 16.9 +/- 0.7 min and were weaned from bypass in < 5 min following ROSC. During the early post-ROSC period, blood flow to the myocardial, cerebral and adrenal vascular beds was significantly elevated relative to baseline. Simultaneously, blood flow to the kidneys, liver, spleen and lungs was reduced relative to baseline. CONCLUSIONS: This low-flow bypass model produces reproducible high resuscitation rates and ROSC times. Early post-resuscitation organ blood flow is characterized by a selective hyperemia involving the cerebral, myocardial and adrenal vascular beds, in contrast to hypoperfusion of the pulmonary and mesenteric vascular beds.

Animals↗

Norepinephrine-induced hypertension following cardiac arrest: effects on myocardial oxygen use in a swine model.

STUDY OBJECTIVE: Recent studies suggest that norepinephrine-induced hypertension early after cardiac arrest ameliorates cerebral hypoperfusion and improves neurologic outcome. The purpose of this study was to evaluate the effects of early norepinephrine-induced hypertension on postresuscitation myocardial blood flow and oxygen use. DESIGN: Prospective, controlled laboratory study. PARTICIPANTS: Ten swine. INTERVENTIONS: All animals underwent 10 minutes of ventricular fibrillation cardiac arrest followed by 5 minutes of low-flow cardiopulmonary bypass (10 mL/kg.min), norepinephrine (0.12 mg/kg), and defibrillation. Animals then were assigned to a hypertension group (mean aortic pressure, 95 mm Hg) or a control group (mean aortic pressure, 75 mm Hg) by titrating a norepinephrine infusion to attain the prescribed aortic pressure. RESULTS: Myocardial blood flow, perfusion pressure, and oxygen metabolism were compared between groups at different times using analysis of variance with a post-hoc Tukey test. Groups had similar myocardial blood flow during ventricular fibrillation, total defibrillation energy, and time to restoration of spontaneous circulation. Fifteen minutes after restoration of spontaneous circulation, the hypertension group had significantly elevated myocardial blood flow, 965 +/- 314 mL/min.100 g versus 325 +/- 67 mL/min.100 g in the control group (P < .001), myocardial oxygen consumption of 51.2 +/- 26.9 mL O2/min.100 g versus 6.4 +/- 3.4 mL O2/min.100 g (P < .001), and myocardial oxygen extraction of 46% +/- 20% versus 14% +/- 4% (P < .01). CONCLUSION: In the early resuscitation period, increasing the norepinephrine dose to induce mild hypertension significantly increases oxygen use in the postischemic myocardium.

Analysis of Variance↗

Predicting oxygenator clinical performance from laboratory in-vitro testing.

Knowledge and predictability of oxygenator performance is vital to safe and effective conduct of cardiopulmonary bypass. The determination of oxygenator performance in the laboratory, however, is carried out under a strict set of conditions established by the Association for the Advancement of Medical Instrumentation (AAMI). This performance data is of limited value in the clinical setting where the perfusionist generally operates outside this set of parameters. This study (1) reports the laboratory performance characteristics of a hollow fiber membrane oxygenator (Sorin Monolyth), (2) uses this data to develop a model to predict performance under a wide range of clinical conditions, (3) compares predicted performance with clinical data collected at two open heart centers, and (4) reviews the complexities of comparing laboratory and clinical performance. An in-vitro "oxygenator-deoxygenator" circuit was utilized to determine O2 and CO2 gas exchange, blood path pressure drop, and heat exchanger efficiency at a variety of blood and gas flows, under standard (AAMI) blood inlet conditions: [table: see text] This laboratory performance data was compared to hospital and computer modeling data. Simple numerical comparison and analysis of variance of regression coefficients over groups indicated that some clinical parameters of performance (oxygen transfer and coefficient of heat exchange) were not predicted with the laboratory data. It is concluded that the laboratory performance data determined under strict controlled conditions may be of limited value in predicting clinical performance unless modeled to allow for variances in operating conditions.

Analysis of Variance↗

Comparative study of five blood cardioplegia systems.

Five blood cardioplegia delivery systems (Gish Straight Shot, Sorin BCD Advanced, Avecor MYOtherm, Baxter-Bentley HE-30, and Baxter-Bentley HE-30 Gold) were evaluated with respect to ease of rapid priming, coefficient of heat exchange, pressure drop, bubble trap capacity, and priming volume. Each system was placed in a roller pump circuit consisting of source and collection reservoirs, cardioplegia solution, and pre-post system pressure and temperature monitoring sites. A trial was performed on four units of each brand by first priming the circuit with 0.9% NaCl at 200 ml/min. Bovine blood (hematocrit 22%) was then introduced simulating use during bypass. Pressure drops across the heat exchanger were measured at flows of 200, 300, and 400 ml/min and at temperatures of 37 degrees, 19 degrees, and 4 degrees C. Coefficient of heat exchange was determined at 300 ml/min flow. Air was infused into the system to quantify the bubble trap capacity of the heat exchanger module. Priming volume of the entire system and of the heat exchanger module were determined by draining each into a graduated cylinder. The Sorin system had significantly less priming volume when compared to all others. The HE-30 units had significantly higher heat exchange coefficients compared to all other systems. Variability was noted in pressure drop at the highest flows and lowest temperatures.

Blood Pressure↗

An automatized computer-method utilizing Procomm Plus and DataEase (4.2) PC and SAS (6.06) mainframe software for isolated, perfused guinea-pig heart studies.

A powerful, time sharing and automatized method of a comprehensive data analysis for isolated, perfused guinea-pig heart studies is described. Data are collected using DataEase PC software (version 4.2) into forms with data fields specified for vital parameters consistently recorded in isolated, perfused heart studies (HR, CBF, PEAKPRESSURE, DPDT, MVO2). After running, DataEase reports the data and information is uploaded to an IBM 3081D mainframe computer on each day of heart experiment and data collection. The uploading process, the data archival and the statistical analyses are automatized by Procomm Plus commands written in Aspect Source Program (.ASP) Files for logging, data transforming and file management procedures. The ASPCOMP.EXE compiler compiles these .ASP files into Aspect Script eXecutable (.ASX) programs, which run on the PC in our laboratory and activate WYLBUR (IBM 3081D Batch-job service and Command file processor) edited files in the mainframe's electronic devices then upload, backup and save data into these files. SAS EXE files containing program instructions for the data analyzing system are then forced by Procomm Plus to operate over the data just uploaded. SAS reads the DATA files by its INFILE facility and performs comprehensive statistical analyses and produces hard output including graphics and JOB reports of dose-response- and logaritmic scale curves for delivery to team members. This computerized and automatized method developed for isolated, perfused guinea-pig heart studies is capable of performing multiple file transfer, sophisticated statistical analyses and graphic procedures after one keystroke on the PC (Alt-F5 in Procomm Plus section) and also facilitates a consistent and convenient method for planning, controlling and standardizing experiments. The method is based on an interactive computer conversation between the PC in the laboratory and the remote's WYLBUR editor. No human presence is needed; however, in case of failure, Procomm Plus gives one of the team members supervising the system a phone call in order to get human help.

Animals↗

Clinical comparisons of continuous venous oxygen saturation and hematocrit monitors in pediatric surgery.

Continuous venous oxygen saturation and hematocrit values are important parameters in assessing patient status while on cardiopulmonary bypass. Two devices used to measure continuous venous oxygen saturation while on cardiopulmonary bypass were compared to a control. The Bentley Oxysat meter and the Medtronic MX2 Oxygen Saturation and Hematocrit System were compared to the ABL500 blood gas monitor. The continuous hematocrit readings from the MX2 system were compared to spun hematocrits. Twenty-nine pediatric patients ranging from 2.3kg-43.3kg were randomly selected. In-line optical transmission cells used were 1/4" or 3/8" depending upon the patient's blood flow requirements. A total of 163 data points were analyzed at different blood flow rates, temperatures, and hematocrits. The venous oxygen saturation values obtained from the Oxysat and the MX2 devices correlated well with the ABL500 over the entire range of blood flows, temperatures, and hematocrits. All correlation coefficients were greater than 0.89. The correlation between the MX2 device and the spun hematocrit varied with temperature ranges. The correlation coefficient tended to decrease with decreasing temperature. We conclude that these devices are important adjuncts to bypass as long as their limitations are understood.

Blood Gas Analysis↗

In vivo validation of a thermodilution system designed to measure peripheral blood flow.

A 5F triple-lumen thermodilution catheter was evaluated in a canine vena cava model to determine whether this catheter and the thermodilution technique provide valid in vivo determinations of blood flow. Our ultimate goal is to develop methods for studying limb blood flow in humans. Seven dogs were studied. Blood flow was provided and regulated by a calibrated roller pump. Flow rate determinations by thermodilution were made over a range of 0.5 to 5.01 1/minute. Excellent correlation (r = 0.98, r2 = 0.96, P less than 0.01) was found between actual flow and flow measured by thermodilution. The mean (+/- SD) coefficient of variation for the thermodilution method was 9.97 +/- 5.72 per cent over the flow range tested. The coefficient of variation tended to be higher at low flow rates. The thermodilution technique with this catheter provides valid in vivo determinations of blood flow through large vessels. This technology can be rationally applied to the study of limb blood flow in humans.

Animals↗