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Biomedical subjects

D R Spahn

Publications and source records attributed to D R Spahn.

15 recordsLinked to original sources

Gas transport during high-frequency ventilation: the significance of direct wash-out.

Gas transport during high-frequency oscillation was investigated in vitro using CO2 elimination from the lung surrogate as a measure of gas transport efficiency. The length of the connecting tube between the piston pump and the three-port connector did not affect gas transport efficiency if the oscillatory volume (VDEL) was constant; inserting an additional tube between the three-port connector and the endotracheal tube decreased gas transport efficiency dramatically. In contradistinction, increasing VDEL caused a steep rise in gas transport efficiency as soon as VDEL surpassed the volume of the tubes connecting the lung surrogate with its surroundings. As gas transport efficiency was found to be very sensitive to the net oscillatory volume, i.e. VDEL minus the volume of the tubes connecting the lung and the surroundings, direct wash-out was considered to be an effective gas transport mechanism during high frequency oscillation. Two preliminary experiments on dogs allowed us to substantiate this hypothesis in vivo.

Animals

Validation of 133Xe clearance as a cerebral blood flow measurement technique during cardiopulmonary bypass.

133Xe clearance to measure cerebral blood flow (CBF) was examined in 10 dogs during cardiopulmonary bypass. As a reference method, a continuous Kety-Schmidt technique (CBFKS) with 133Xe as indicator was used. Extracranial tissue was removed to directly place the 133Xe detectors on the skull, and the head was covered with a 3 mm lead shield to minimize contamination of the 133Xe clearance curve with extracranial radiation. 133Xe detectors for the Kety-Schmidt technique were embedded in a shielded brass block to minimize interference with radiation from the animal's body. 133Xe clearance data were analyzed using stochastic (CBF10, CBF15, and CBFINF) and initial slope methods (CBFIS), and the results were compared with CBFKS using linear regression. CBF15 and CBFINF yielded similar CBF values as CBFKS (CBFKS = 0.97.CBF15-2.08, r = 0.92, p less than 0.01; CBFKS = 1.13.CBFINF-1.21, r = 0.92, p less than 0.01). CBF10 slightly overestimated CBFKS but still showed a close correlation to CBFKS (CBFKS = 0.89.CBF10-2.58, r = 0.92, p less than 0.01) and CBFIS considerably overestimated CBFKS (CBFKS = 0.60.CBFIS-1.27, r = 0.87, p less than 0.01). With extracranial contamination of the 133Xe clearance curve minimized, all 133Xe clearance techniques used to measure CBF were consistently related to CBFKS in a constant, significant manner. 133Xe clearance therefore is a valid method to assess CBF during cardiopulmonary bypass.

Animals

Perioperative myocardial ischemia and infarction. Prophylaxis and treatment of ischemia.

Protection from and treatment of myocardial ischemia involves detection and recognition of early changes in myocardial function associated with ischemia, as well as use of techniques and agents designed to alleviate or ameliorate ischemia. However, decisions regarding which agent(s) to employ depend upon not only the effects of a particular therapy but also the interaction(s) among the therapeutic agents and anesthetics. All the drugs and treatments discussed above may have beneficial effects in conscious patients but variable degrees of effectiveness during anesthesia. The choice of agents to be used for myocardial protection ultimately depends upon clinical decisions regarding coronary blood supply and myocardial oxygen demand. The availability of several different classes of agents capable of altering specific physiological variables allows a wide variety of clinical situations to be effectively managed.

Cardiotonic Agents

Effects of acute isovolemic hemodilution and anesthesia on regional function in left ventricular myocardium with compromised coronary blood flow.

The effects of progressive, isovolemic hemodilution using Dextran 70 and the effect of halothane (0.7, 0.9, 1.1, and 1.3% end-tidal, administered randomly at each level of hemodilution) on global cardiovascular and regional LV contractile functions were investigated in 24 dogs with induced critical constriction of the left anterior descending coronary artery (LAD). Two additional groups of six dogs each (with and without LAD stenosis) not undergoing hemodilution served as time controls. Regional LV contractile function was assessed by sonomicrometry in the flow-compromised apical LAD territory, as well as in three non-compromised LV areas supplied by the left circumflex coronary artery. Regional myocardial function was found to be stable throughout the study period of 4-5 h in both time control groups. Mean arterial and coronary perfusion pressures as well as LV dP/dtmin decreased (P < 0.01) during hemodilution. LV dP/dtmax remained unchanged, and heart rate and LVEDP increased slightly (P < 0.05). Systolic shortening (SS) in the LAD territory was unchanged at a hematocrit (HCT) of 33.5 +/- 0.3% (mean +/- s.e. mean), and decreased marginally at an HCT of 24.2 +/- 0.1% (SS of 17.4 +/- 1.0% as compared to 20.2 +/- 1.6% at critical constriction (CC), P < 0.05). No increase in post-systolic shortening (PSS) occurred in the compromised area. Severe LAD dysfunction was observed in the LAD territory at an HCT of 14.9 +/- 0.1%, as systolic shortening decreased (11.8 +/- 1.1%, P < 0.01 vs CC) and PSS increased (31.2 +/- 3.4%, P < 0.01 vs CC). The effects of hemodilution on global cardiovascular and regional myocardial functions were unaffected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General

Influence of anesthesia on the threshold of pacing-induced ischemia.

Increased myocardial oxygen demand, induced by increased heart rate, may cause myocardial ischemia in the presence of significant coronary artery disease. Alterations in anesthetic depth or technique might put at risk or protect myocardium with compromised blood flow. In 20 dogs with critical left anterior descending coronary artery (LAD) stenosis, atrial pacing rates from 100 to 160 beats/min were achieved, with end-tidal halothane 0.7% (LowH) and 1.1% (HighH), end-tidal isoflurane 1.1% (LowI) and 1.5% (HighI), as well as with continuous fentanyl plus midazolam (FM) infusion anesthesia. Despite significantly different mean arterial and coronary perfusion pressures, rate-pressure product, and left ventricular dP/dtmax, the pacing rate at which systolic shortening decreased below the lower limit of the physiologic response, indicating regional dysfunction, was the same in all investigated anesthesia conditions (LowH: 127 +/- 4 beats/min; HighH: 128 +/- 5 beats/min; LowI: 125 +/- 4 beats/min; HighI: 122 +/- 5 beats/min; FM: 124 +/- 4 beats/min [mean +/- SEM], P greater than 0.05). None of the investigated anesthesia conditions either increased ischemia tolerance or showed a detrimental effect on myocardium with compromised coronary blood flow.

Animals

Significance of bulk convection during high-frequency oscillation.

In 7 anesthetized supine dogs with an anatomic dead space of 115-162 ml, gas transport during high-frequency oscillation (HFO) was investigated at an oscillatory frequency of 15 Hz. Starting with an oscillatory volume effectively delivered to the lungs (VDEL) of 60 ml, measured on line with an ultrasonic airflow meter, VDEL was reduced in steps of 10 ml, down to a VDEL of 30 ml, whereby fresh gas flow rate, airway occlusion pressure and lung volume above functional residual capacity were kept constant. An HFO-circuit without bias tube was used. The volume of endotracheal tube and three port connector, designated as HFO-circuit related rebreathing volume, was 35 ml. PaCO2 continuously increased, when VDEL was reduced from 60 ml to 40 ml and the data fit perfectly to a reciprocal regression (1/PaCO2 = a + b.VDEL), r2 ranging from 0.95 to 1.00. Measured PaCO2 values at a VDEL of 30 ml (8.26 +/- 1.77 kPa), however, were significantly (P less than 0.025) higher than PaCO2 values predicted by the individual reciprocal regression equations (6.25 +/- 1.46 kPa). This overproportionate increase in PaCO2 due to a reduction of VDEL from 40 ml to 30 ml may be explained by the sudden drop out of bulk convection as a gas transport mechanism between central airways and the surrounding because bulk convection is only possible as long as VDEL exceeds the HFO-circuit related rebreathing volume. Bulk convection therefore is considered an essential gas transport mechanism during HFO and the efficiency of CO2 elimination during HFO is critically dependent on the net oscillatory volume, i.e. VDEL minus the HFO-circuit related rebreathing volume and not on the relationship between VDEL and anatomic dead space.

Animals

Desensitization of myocardial beta-adrenergic receptors during cardiopulmonary bypass. Evidence for early uncoupling and late downregulation.

BACKGROUND: Cardiopulmonary bypass (CPB), a process routinely used during cardiac surgery, is a potent stimulant to the release of endogenous catecholamines. Hence, we tested the hypothesis that CPB results in myocardial beta-adrenergic receptor (beta AR) desensitization. METHODS AND RESULTS: We obtained canine transmyocardial left ventricular biopsies before, during (155 minutes), and after CPB (pre-CPB, CPB, and post-CPB, respectively) and determined beta AR density, proportion of beta 1AR to beta 2AR, and beta AR coupling capacity to adenylyl cyclase. Beta AR density was stable at 112 +/- 14 fmol/mg (pre-CPB) and 103 +/- 9 fmol/mg (CPB) but decreased post-CPB to 84 +/- 7 fmol/mg. The ratio of beta 1AR to beta 2AR (determined by two-site fit for [125I]-iodocyanopindolol competition binding with the beta 1AR selective antagonist ICI89.406) remained constant throughout (60 +/- 3: 40 +/- 3 pre-CPB, 55 +/- 3: 44 +/- 3 CPB, and 61 +/- 2: 39 +/- 2 post-CPB), revealing that both beta 1AR and beta 2AR subtypes were downregulated. A different pattern was noted in the functional properties of these receptors during CPB. Decreased maximal isoproterenol-stimulated adenylyl cyclase activity (252 +/- 14 to 216 +/- 12 pmol/30 min/mg), submaximal isoproterenol-stimulated adenylyl cyclase activity (183 +/- 10 to 157 +/- 11 pmol/30 min/mg), and zinterol-stimulated adenylyl cyclase activity (187 +/- 11 to 159 +/- 11 pmol/30 min/mg, a measure of beta 2AR subtype activation) were noted during CPB, at the time when weaning from CPB takes place. However, this desensitized pattern was found to be completely reversed by 30 minutes post-CPB, with adenylyl cyclase activities returning to pre-CPB levels or slightly higher. Control dogs that did not receive CPB showed no change in beta AR density or adenylyl cyclase activity. CONCLUSIONS: These data suggest that myocardial beta AR desensitization does occur during CPB in healthy, nonischemic canine myocardium and that this pattern is reversed 30 minutes after discontinuation of CPB. In addition, a slower process of beta AR downregulation persists after discontinuation of CPB. Because successful weaning from CPB is a critical process during myocardial surgery, these findings have potentially important implications in the management of such patients.

Adenylyl Cyclases

Effects of cardiopulmonary bypass and cardioplegia on regional and global cardiac actions of halothane in dogs.

Cardiopulmonary bypass (CPB) with aortic cross-clamping represents a controlled period of global cardiac ischemia. We hypothesized that CPB (asanguineous prime), with aortic cross-clamping and repeated cardioplegia, alters myocardial function, which would be manifested as an exaggerated myocardial depression caused by halothane after CPB. In nine dogs anesthetized with fentanyl and midazolam, halothane dose-response curves (0.0%-2.0%) were compared before and after CPB. A reduced mean arterial blood pressure (46.4 +/- 3.7 vs 85.8 +/- 5.9 mm Hg), associated with a marked hemodilution (hematocrit, 19% +/- 1% vs 41% +/- 2%), was observed after CPB. Cardiac output and systolic shortening were not significantly different after versus before CPB during fentanyl-midazolam anesthesia. Normalized to fentanyl-midazolam hemodynamics, halothane dose-response curves before and after CPB were identical for all variables except cardiac output, where halothane caused a slight but statistically significantly more pronounced decrease after CPB compared with before CPB. The effect of halothane on left ventricular function, therefore, is relatively unaffected by CPB with cardioplegia.

Animals

Gas transport enhancement in high-frequency oscillation.

Gas transport during high-frequency oscillation (HFO) with (HFO+BT) and without bias tube (HFO-BT) was investigated in 10 anesthetized supine dogs. The oscillatory volume effectively delivered to the lungs, airway occlusion pressure and lung volume above functional residual capacity (FRC), regulated by a newly deviced pressure control system, as well as the oscillatory frequency (20 Hz) were adjusted to equal levels in HFO+BT and HFO-BT. At a fresh gas flow rate (fgf) of 3 L/min (room air), arterial CO2 partial pressures (PaCO2) decreased from 49.9 +/- 6.5 mm Hg (mean +/- SD) to 40.2 +/- 6.3 mm Hg (P less than 0.01) i.e. by 19.2 +/- 8.7%, and arterial O2 partial pressures (PaO2) increased from 71.5 +/- 13.1 mm Hg to 85.6 +/- 14.6 mm Hg (P less than 0.01) or by 20.5 +/- 12.0% in HFO-BT as compared to HFO+BT. At a fgf of 6 L/min, PaCO2 decreased less but still significantly (P less than 0.025) from 42.1 +/- 6.5 mm Hg to 37.8 +/- 6.8 mm Hg (10.4 +/- 5.6%) and PaO2 increased from 78.1 +/- 12.9 mm Hg to 84.6 +/- 16.4 mm Hg i.e. by 8.1 +/- 6.4% (P less than 0.05) in HFO-BT. The higher gas transport efficiency after removing the bias tube can be explained by two mechanisms: (1) By removing the bias tube, the volume of the bias system decreased from 54 ml in HFO+BT to 1 ml in HFO-BT and rebreathing of exhaust gas from the bias system is therefore eliminated in HFO-BT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Noninvasive versus invasive assessment of cardiac output after cardiac surgery: clinical validation.

The accuracy of noninvasive cardiac output (CO) measurement techniques, such as electrical bioimpedance (BIO), suprasternal continuous-wave Doppler (CWD), pulsed-wave Doppler (PWD), and transesophageal continuous-wave Doppler (TED) ultrasound has been variably judged in recent years. In addition, clinical comparisons are hampered by the fact that there is no generally accepted gold standard in CO measurement. After coronary artery bypass surgery in 25 patients, CO was simultaneously determined by invasive standard techniques (thermodilution [TD] and Fick methods) plus BIO, CWD, PWD, and TED. There was an excellent agreement found between TD and the Fick method (COF = 0.13 + 1.01.COTD; r = 0.96; n = 99). Thermodilution was thus chosen to be the reference method. Bioimpedance underestimated COTD (COBIO = 0.47 + 0.60.COTD; r = 0.78; n = 111). Allowing physiological ejection times only led to an improved agreement between BIO and TD (COBIO = 0.05 + 0.69.COTD; r = 0.82; n = 79), but BIO still significantly underestimated COTD (P less than 0.0005). Using physiologic ejection times during COCWD determination reduced the scatter of data as compared with TD; however, CWD still considerably overestimated COTD, when COCWD computation was based on the echocardiographic aortic diameter (ECHO) (COCWD ECHO = 0.79 + 1.40.COTD; r = 0.84; n = 52). With the surgical aortic diameter (SURG), the agreement improved (COCWD SURG = 0.75 + 1.16.COTD; r = 0.89; n = 44), but overestimation of COTD remained significant (P less than 0.05). Irrespective of the aortic diameter, COPWD values showed a considerable scatter of data compared with COTD (COPWD ECHO = 1.26 + 0.60.COTD; r = 0.62; n = 64 and COPWD SURG = 1.42 + 0.41.COTD; r = 0.47; n = 61). Correlation of absolute COTED values to thermodilution depended on the method used for calibration. All investigated noninvasive CO measurement techniques unreliably measured relative CO changes. Despite its invasiveness, TD remains the method of choice for accurate CO determination in adult patients following cardiac surgery.

Adult

Augmentation of CO2 elimination during high frequency oscillation by removing the bias tube--an in vitro study.

In clinical applications of high frequency oscillation (HFO), sufficient CO2 elimination (VCO2) may represent a problem mainly at higher oscillation frequencies. With the intention of examining how to increase VCO2 a modified bias flow system was investigated in vitro with wash-out experiments. In bias flow systems, long tubes have been used in order to minimize the loss of oscillatory volume; however, a distinct increase of VCO2 was achieved in the present study by removing the bias tube. This improvement occurred over the whole frequency range of 2-60 Hz, although the oscillatory volume, effectively delivered to the lungs was smaller with the HFO circuit without bias tube (HFO-BT) as compared to the arrangement with bias tube (HFO + BT). A long bias tube flattens the CO2 concentration gradient from the alveoli to the atmosphere. Removing the bias tube results in a steeper CO2 concentration gradient and in a correspondingly enhanced VCO2. Furthermore, the large oscillatory volume at the exit of the bias flow system in HFO-BT supports VCO2 as an additional wash-out mechanism. Based upon longitudinal tracer gas concentration measurements between the alveoli and the atmosphere during HFO16,17, an increase of gas transport up to 20% can be expected for in vivo applications by removing the bias tube.

Carbon Dioxide

Lung surrogates.

In the development and evaluation of mechanical ventilation on the basis of high-frequency oscillation, appropriate surrogates of the lung are important, because they allow the measurement and control of various parameters which are not accessible in animal models. Yet, criteria have to be established according to which results obtained with a surrogate may be assessed with a view to extrapolation to humans. Theoretical considerations and impedance measurements are used for this purpose. It is found that for each given frequency a model can be made which exhibits realistic properties. However, no uniformly valid surrogate in the entire frequency range of 10-50 Hz is available at present.

Animals

Flow separation, an important mechanism in the formation of mean pulmonary pressure during high-frequency oscillation.

Mean pressures within the lungs and lung volume, respectively, are clinically important parameters. During ventilation by way of high-frequency oscillation (HFO), these parameters have been shown to be strongly frequency dependent. To identify mechanisms leading to mean pressure formation during HFO, findings of the theory of stationary flow were extended to oscillatory flow by a quasi-stationary approach. To confirm the theoretical findings, in-vitro experiments on HFO-models were performed. Flow separation was found to be an important mechanism in the formation of mean pressure. Flow separation causes a significant flow resistance, which may be distinctly different for in- and outflow. During oscillatory flow, a mean pressure difference thus results. This mechanism is of particular importance in bifurcations, which are present in the HFO-circuit as well as in the airways. With the direction-dependent flow separation, a general mechanism was found, which accounts for differing mean pressure values within the lungs with different HFO-circuits. This mechanism also contributes to interregionally different mean pressure values within the lungs.

High-Frequency Ventilation