Continuous In-Line Monitoring of Oxygen Delivery to Control Artificial Heart Output

In order to evaluate the pump output control based on the oxygen delivery to peripheral tissues, arterial and mixed venous hemoglobin content ([Hb]) and oxygen saturation (SO2) were continuously monitored in three biventricular bypass animals (3-, 6-, and 40-day experiments) with fibrillating ventricles. The specially developed oxygen sensors were mounted in the outflow ports of the artificial hearts to measure [Hb] and SO2. One animal was exercised on the treadmill at 2.0 mile/h for 15 min with pump flows fixed to deliver oxygen of (a) above 13 cc/min/kg, (b) 10, and (c) 9. In (a), the mixed venous saturation (SvO2) dropped to approximately 25% with no increase in the blood lactate level. In (b) and (c), the SvO2 decreased to approximately 10-15% with increase in blood lactate levels from 4 to 10-30 mg/dl. Also, the recovery of the SvO2 in these groups following the termination of the exercise was slower in comparison to (a). The lower limit of the SvO2 level that would create oxygen debt situation in the peripheral tissues was approximately 25-30% for the exercise of 2.0 mile/h. The SvO2 reflects changes in respiratory status, pump output, hemoglobin level, and metabolism, and is thus a useful indicator to diagnose quickly the circulatory status as well as possibly to control the artificial heart output.     

Do changes in carhiac output affect the inspiratory to end-tidal oxygen dfference?

Background. The paramagnetic technique has made it possible to monitor the end-tidal oxygen concentration and P_(I-ET)O₂, i. e. inspiratory to end-tidal oxygen difference, breath-by-breath. Little is known about the implications of a changing P_(I-ET)O₂, but so far studies have shown it to be a quick and sensitive variable to detect hypoventilation. This study was designed to observe the circulatory effects on P_(I-ET)O₂ in an experimental setting but monitored as in a clinical situation.
Methods. We assessed the oxygen difference during changes in cardiac output induced by intravenous ephedrine-hydrochloride in 12 healthy male volunteers. P_(I-ET)O₂ was measured with a fast-response paramagnetic differential oxygen sensor. Cardiac output was measured with non-invasive transthoracie electrical bioimpedance. As stimultaneous changes in metabolism and ventilation will also influence P_(I-ET)O₂, oxygen uptake and expired minute volume were monitored. After a rest period, the subjects had an intravenous injection of ephedrine-hydrochloride 0.1 mg·kg^-1 followed by a 30-min observation period.
Results. Cardiac output increased significantly as did the oxygen uptake and the ventilation. We found no biologically significant correlation between cardiac output and P_(I-ET)O₂. The P_(I-ET)O₂ was influenced by ventilation and metabolism.     

Classes of tissue hypoxia

We identify eight causes of tissue hypoxia, falling into three classes, A, B, and C, depending upon the effect on the critical mixed venous p O₂ and the optimal oxygen consumption rate. The critical mixed venous p O₂ is the value above which the oxygen consumption rate is optimal and independent of the mixed venous p O₂ and below which the oxygen consumption rate decreases towards zero. Class A hypoxia: primary decrease in mixed venous p O₂. Causes: 1) ischaemic hypoxia (decrease in cardiac output), 2) low-extractivity hypoxia (decrease in oxygen extraction tension, p ₈). Class B hypoxia: primary increase in critical mixed venous p O₂. Causes: 1) shunt hypoxia (increased a-v shunting), 2) dysperfusion hypoxia (increased diffusion length from erythrocytes to mitochondria and/or decreased total capillary endothelial diffusion area, e. g., tissue oedema, microembolism), 3) histotoxic hypoxia (inhibition of the cytochrome chain). Class C hypoxia: primary increase in optimal oxygen consumption rate. Causes: 1) uncoupling hypoxia (uncoupling of the ATP formation associated with O₂ reduction), 2) hypermetabolic hypoxia (increased energy metabolism, e. g., due to hyperthermia).     

α1-adrenoceptor stimulation is able to reverse halothaneinduced cardiac depression in isolated rat hearts

Background: Stimulation of myocardial α₁-adrenoceptors has been shown to exert positive inotropic effects through a cyclic AMP-independent mechanism. The purpose of this study was to examine if α₁-adrenoceptor stimulation is able to attenuate myocardial depression produced by exposure to halothane, and to test if α₁-adrenoceptor stimulation alters myocardial oxygen supply-demand balance in hearts exposed to halothane.
Methods: The effects of phenylephrine were examined in 7 isolated perfused rat hearts. Variables measured were: heart rate, isovolumetric peak left ventricular pressure (LVP), LV dP/dt, coronary arterial flow, myocardial O₂ delivery (DO₂), myocardial O₂ consumption (MVO₂) and the ratio of DO₂/MVO₂. Each heart was exposed to phenylephrine cumulatively 0.1 μM, 0.3 μM, 1 μM and 3 μM under the administration of 1% halothane in the presence of propranolol 1μM.
Results: Halothane 1% decreased the heart rate by 9±3%, LVP by 37±3%, and LV dP/dt by 35±2%. Phenylephrine restored these decreases to the baseline levels. Phenylephrine maintained or further enhanced the reductions in coronary flow and DO₂ produced by halothane, resulting in a decrease in the DO₂/ MVO₂ ratio.
Conclusion: α₁adrenoceptor stimulation is capable of restoring direct cardiac depressant effects of halothane with a possible impairment of the oxygen supply-demand balance.     

Alfentanil and Skeletal Muscle Circulation, Oxygen Consumption and P50

The preservation of blood flow to skeletal muscles has low priority in the intact organism. If cardiovascular function is disturbed, for example by anesthetic drugs, skeletal muscle circulation diminishes or stops. Skeletal muscle surface pH (m-pH) is a sensitive indicator of muscle cell oxygenation and a fall in m-pH therefore provides an early warning of deterioration in overall cardiovascular performance. In the present study we investigated the peripheral effects of a new short-acting fentanyl derivative, alfentanil. Twelve dogs were anesthetized with a bolus injection of alfentanil 0.16 mg-kg^-1 i.v. M-pH was recorded continuously, while total body oxygen consumption, oxygen transport and P50 were calculated. No changes were found. In the second part of the study, we pretreated six of the dogs with the "calcium antagonist" verapamil 0.5 mg-kg^-1, while the other six dogs served as controls. After a rechallenge dose of alfentanil, we again found the peripheral perfusion sufficient to meet the oxygen demand of the muscles. Side-effects to alfentanil were a decrease in Pao₂, due to an increase in pulmonary shunting of venous blood, and an increase in Paco₂. The changes in pulmonary ventilation-perfusion relationships were, however, not of a magnitude that should cause concern when alfentanil is used in normal subjects.     

Effects of Nitroglycerin on Central Haemodynamics and VA/Q Distribution Early after Coronary Bypass Surgery

Central haemodynamics and ventilation-perfusion (_AA/) distributions were studied in nine patients, 21 h after coronary bypass surgery, before and during nitroglycerin (TNG) infusion. _A/ distributions were established with the multiple inert gas elimination technique of Wagner and West. Administration of TNG resulted in a decrease in mean arterial pressure, a slight reduction in cardiac output and stroke volume and a significant increase in heart rate, possibly explained by an initial relative hypovolaemia. Pulmonary arterial pressures and filling pressures for the right and left ventricles decreased significantly. There was a significant reduction in Pao₂ and an increase in venous admixture (_VA/_T) from 11.3 to 16.5% of cardiac output. This was mainly due to an initial SF₆-shunt of 6.4% increasing to 12.8%. Only 3.5% of cardiac output during TNG was due to perfusion of hypoventilated areas. The mean for the control -distribution was 0.88 with a mean log s.d. of ±1.14, indicating _A/-mismatch and did not change significantly. The reduction of pressures in the pulmonary vascular bed was accompanied by increased ventilation of areas with high _A/.     

Estimation of Blood Flow in Transcutaneous PO2 Measurements

A method for estimation of the cutaneous blood flow in transcutaneous Po₂ measurements is presented. Recordings of electrode and skin temperature make it possible to compute the effect dissipated to the circulating blood. Eighteen measurements were performed on three healthy volunteers at electrode temperature settings from 37.0°C to 45.0°C. The blood-flow estimates ranged from 0.07 to 0.19 ml·cm^-2·min^-1. At an electrode temperature of 45.0°C the investigations showed a tc-Po₂ value as low as 7 mmHg (0.9 kPa) which, however, corresponded well to the lowest blood-flow estimate determined. The temperature-corrected (37°C) a-Po₂-tc-Po₂ gradient ranged from 50 mmHg to 95 mmHg (6.7–12.6 kPa). The investigations confirm the importance of simultaneous determinations of cutaneous blood flow, capillary temperature and cutaneous oxygen consumption in order to describe the connection between arterial and cutaneous oxygen tension. The cutaneous blood How seems in this connection to be the most important parameter.     

Clinical assessment of oxygen delivery and consumption during hypotensive anaesthesia - A clinical application of The Deep Picture™

Usual evaluation of the relationship between oxygen delivery (DO₂) and oxygen uptake (VO₂) is based on the arterial oxygen tension (pO₂), oxygen saturation (sO₂), haemoglobin concentration (ctHb), the same indicators in mixed venous blood and cardiac output, sometimes supplemented by the expiratory carbon dioxide concentration. And, so far, the relationship among DO₂, VO₂ and the new parameters for an evaluation of oxygen status (oxygen extraction tension: p_K, concentration of extractable oxygen: c_x, oxygen compensation factor: Q_x) (1) has not been discussed enough.
Therefore, this study was designed to evaluate whether the new parameters give the clinically significant information to analyse the relationship between DO₂ and VO₂ during the acute haemodynamic change with intentionally induced hypotension in anaesthetized adult patients.     

Studies on the oxygenation of human blood by photocatalytic action

Abstract:  The present article gave the proof of concept for oxygenating human blood using the established principles of photocatalytic action of anatase TiO₂ thin films in generating oxygen from water. The photocatalytic action involves the absorption of the UV optical energy (365 nm) to split water available in the blood into oxygen and hydrogen, and the generated oxygen is attached to the hemoglobin. In the present study, an enhanced catalytic action was achieved by preparing the nanosized anatase TiO₂ thin films on tin-doped indium oxide (ITO) thin films, forming TiO₂/ITO semiconducting junction. These TiO₂ and ITO thin films and the semiconducting junctions were grown by the reactive DC Magnetron sputtering technique (using pure metallic targets) at room temperature (300 K) and subsequently annealed at 870 K for 60 min. The annealing process (i) influenced the formation of the anatase phase of TiO₂; and (ii) diffused indium from ITO into TiO₂, forming InTi₂O₅. The work functions of ITO and InTi₂O₅ were measured to be 4.72 and 4.76 eV, respectively. The higher efficacy of the photocatalytic action was attributed to the lower work function of ITO. The results clearly show that the photocatalytic action increases the oxygen content in the blood significantly.     

Sweep Gas Flowrate and C02 Exchange in Artificial Lungs

Abstract A simple analysis and graphic result are presented for characterizing the dependence of CO₂ exchange on the sweep gas (ventilating gas) flowrate in artificial lungs. The analysis requires no knowledge of the device-specific mass transfer characteristics of an artificial lung, nor does it require detailed mathematical modeling or computer simulation. Rather, it uses appropriate normalization to establish generic features of the gas flow dependency of CO₂ exchange that are applicable to all artificial lung devices. Principal results are that the transition from relatively gas flow-sensitive to gas flow-insensitive CO₂, exchange occurs at sweep gas flowrates of approximately 40–60 times the CO₂ exchange rate. Achieving a CO₂ exchange rate within 85% of maximal (for a given oxygenator and blood-side conditions) requires a sweep gas flowrate of no less than approximately 50 times the nominal CO₂ exchange rate. When the sweep gas flowrate is less than 20 times the CO₂ exchange rate, CO₂ exchange is highly gas flow dependent and less than one-half the maximal possible rate.     

A maximal central venous oxygen saturation (SvO2max) for the surgical patient

Before induction of anaesthesia, 23 patients scheduled for major abdominal surgery had blood samples drawn from a central venous catheter for oxygen saturation (SvO₂) after graded infusion of isotonic saline. The infusion of saline was continued until further administration resulted in a stable SvO₂ (SvO₂max). The SvO₂ increased from 69 (53–83) to 72 (66–83) % (median and range; P < 0. 0001), when the patients received 10 (0–26) mL- kg^-1, average 500 mL, of saline. At the same time central venous haematocrit decreased from 38 (32–47) to 36 (23–47) % which suggests that the intravascular volume was expanded by 420 (180–3070) mL or by 72 (18–174) % of the administered volume. The results demonstrate that volume expansion by saline can establish a maximal venous oxygen saturation in the surgical patient.     

Monitoring of Optimal Oxygen Transport by the Transcutaneous Oxygen Tension Method in the Pig

The validity of the transcutaneous oxygen tension (Ptco₂) method as opposed to measurement of arterial oxygen tension (Pao₂) and mixed venous oxygen saturation (SO₂), for monitoring optimal oxygen transport, was studied in six mechanically ventilated pigs with an oleic acid lung injury. With stepwise increments in positive end-expiratory pressure (PEEP) from zero to 20 cmH₂O, maximum oxygen flux was found at a PEEP of 8 cmH₂O and named "optimal PEEP". With increasing PEEP, cardiac output (CO) was maintained up to a PEEP of 8 cmH₂O, when it began to decline, while venous admixture decreased at all respiratory settings up to a PEEP of 16, when it was about one-fourth of the value (38.7%) at a PEEP of zero. Pao₂ increased with rising PEEP and reached a steady level at a PEEP of 16 cmH₂O. Ptco₂ and SO₂ parallelled each other and rose steeply up to a PEEP of 8 cmH₂O. They showed a further slight increase up to a PEEP of 12 and alter that a tendency to decrease. It is concluded that Ptco₂ and So₂ both seem to distinguish the optimal PEEP and give more adequate information than does Pao₂. The Ptco₂ method has the advantage of being non-invasive.     

Intraarterial Perfusion of the Hindlimb with Pyridoxalated Hemoglobin Polyoxyethylene Conjugate Solution in Anesthetized Dogs

Abstract: To evaluate the potential clinical usefulness of a modified hemoglobin, pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), the hindlimb vascular bed was perfused with PHP solution while monitoring tissue oxygen tension (Pto₂) in anesthetized dogs. The hindlimb region was perfused through the external iliac artery with a roller pump at a varying perfusion rate. Pto₂ was measured using a Po₂-monitoring probe inserted into the gra-cial muscle. After surgical preparation for perfusion, the iliac arterial flow rate was 19.9 ± 5.6 ml/min, and baseline Pto₂ was 38.4 ±1.3 mm Hg. Perfusion with autologous arterial blood with the pump increased Pto₂ and perfusion pressure (PP) in a perfusion rate-dependent manner. Perfusion with PHP solution at 20 ml/min decreased Pto₂ from the initial baseline level, but an increase in the flow rate to 40–55 ml/min restored or induced an elevation of Pto₂. Results demonstrated that PHP solution can deliver oxygen to local tissue and maintain tissue oxygen tension at the same level as autologous arterial blood at a high enough flow rate.     

Respiration, Circulation and Anaesthetic Management in Obesity. Investigation before and after Jejunoileal Bypass

Some ventilatory and circulatory parameters were studied in 17 very obese patients before and after weight reduction following jejunoileal bypass. A low vital capacity and signs of impaired lung function with intrapulmonary shunting, increased alveolar-arterial Po₂ difference and low Pa_o2 were found. Although the spirometric values improved significantly after weight reduction, the ventilatory disturbance persisted. A normal response to inhalation of CO₂ was seen. The total blood volume was high and did not change after weight reduction. However, if calculated as blood volume per kg body weight, the values were lower than normal, and they increased as a consequence of weight reduction. Cardiac output was slightly lower than normal in relation to oxygen consumption. Total peripheral resistance was normal. Arterial blood pressure, which was in the high normal range preoperatively, decreased significantly after weight reduction. Total doses of intravenous anaesthetic agents and muscle relaxants were the same as for patients of normal weight. The importance of preoperative evaluation and of respiratory care of obese patients undergoing elective surgery is stressed.     

The Effect of Respiratory Frequency on Pulmonary Function During Artificial Ventilation

This is a review of previous studies on the effects of variations between 12 and 24 breaths per minute in ventilation frequency during artificial ventilation, minute ventilation being constant. The total material consisted of 66 healthy subjects investigated under anaesthesia with artificial ventilation and 43 patients investigated during prolonged respiratory treatment. An increase in ventilation frequency resulted in an increased ratio of dead space to tidal volume (V_D/V_T,) and in diminished alveolar ventilation with a subsequent elevation of Paco₂. The pressures in airways and alveoli were lowered. The dynamic compliance both of the lungs and of the chest wall was diminished and inspiratory resistance was slightly reduced. Intrapulmonary gas distribution was unaffected. Cardiac output was increased, as was venous admixture. Pao₂ was slightly reduced. The more efficient gas exchange occurring at a low ventilation frequency makes this setting preferable in the treatment of patients with chronic obstructive lung disease, whereas a high ventilation frequency, by improving cardiac output, may be advantageous in patients with circulatory failure.     

Evaluation of Platelet Adhesion and Activation on Materials for an Implantable Centrifugal Blood Pump

A totally implantable centrifugal artificial heart has been developed in which a pivot bearing supported centrifugal pump is used as a blood pump. The following have been adopted as blood contacting materials in our pump: titanium alloy (Ti-6Al-4V) for the housing and impeller, alumina ceramic (Al₂O₃) for the male pivots, and ultrahigh molecular weight polyethylene (PE) for the female pivots. Greater antithrombogenicity is required for an implantable blood pump. To examine the thrombogenicity of these materials, we evaluated in vitro platelet adhesion and activation, which may play key roles in thrombogenesis on foreign surfaces. Ti-6Al-4V, Al₂O₃, and PE were compared with polycarbonate (PC), silicone carbide (SiC), and pure titanium (pTi). Platelet adhesion was assessed using monoclonal antibody (CD61) directed against glycoprotein IIIa. Platelet activation was evaluated by measuring P-selectin (GMP-140) released from irreversibly activated platelets. Each material with a surface area of 16.6 cm² was incubated with 2.5 ml of plasma or 2.5 ml of heparinized fresh whole blood for 3 h at 37°C. The optical density (OD) at a wavelength of 450 nm for CD61 was 0.93 ± 0.35 in PC, 0.34 ± 0.13 in PE, 0.27 ± 0.13 in pTi, 0.26 ± 0.01 in Al₂O₃, 0.21 ± 0.04 in SiC, and 0.12 ± 0.12 in Ti-6Al-4V. The GMP-140 levels of the tested materials were not significantly different from the control value (45.9 ± 7.2 ng/ml). These results indicate that Al₂O₃, PE, and Ti-6Al-4V, which are incorporated into our implantable centrifugal pump, have satisfactory antithrombogenic properties in terms of platelet adhesion. However, platelet activation by any material was not observed under the static condition in this study.     

Problems of Calibration and Stabilization of tcPo2 Electrodes

The stirring effect factor Ø, used to correct tcP_o2 readings for the gradient of P_o2 induced in skin by electrode O₂ consumption, was measured with 20 μm cathode electrodes at 44C for various membrane, spacer and electrolyte combinations. Two in vitro models closely resemble skin Ø values: (1) 50% ethylene glycol/water equilibrated with air at 44C, compared to air above this liquid; (2) a mock skin consisting of 25 μm Teflon on foam rubber, in air, dry. Ø varied from 1.01 with 22 μm polypropylene over a 12 μm cellophane spacer, with either aqueous or nonaqueous, chloride-free alkaline electrolyte, to more than 1.10 when 25 μm Teflon was tested without a spacer. Ø may be predicted: Ø = 1+ 0.44 i/(M + 10C + 20) where i is pA/mmHg electrode sensitivity, and M and C are membrane and cellophane thickness, μm. Pressure sensitivity, tested against foam rubber, was minimized by use of a spacer, and often increased with age of Teflon membrane. Drift may result from water vapour movements across membranes if calibration media have P(H20) either too high or too low. Minimum drift on skin was seen after electrode equilibration with P(H₂0) = 58 mmHg. Drift on skin is also caused by a slow effect of P_co2 on reference electrode potential, and this is minimized by buffering electrolyte with K₂B₄O_7.     

The Influence of the Ventilatory Pattern on Ventilation, Circulation and Oxygen Transport during Continuous Positive-Pressure Ventilation An Experimental Study

In IPPV, the ventilatory pattern produced by the ventilator and the lung systems is known to influence pulmonary and cardiovascular functions. In this study on dogs the ventilatory pattern of a conventional respirator (Siemens-Elema Servo Ventilator 900=SV-900) constituted the norm for comparison with that produced by a system for volume-controlled HFPPV. The experimental conditions were kept identical (pentobarbital anaesthesia and normoventilation, i.e. arterial P_CO2=40 mm Hg, pH=7.4 and constant F_IO2 of the inspired air).
At comparable alveolar ventilation the intratracheal peak and mean pressures were always higher during ventilation with SV-900 than during HFPPV. The calculated alveolar oxygen partial pressure (P_AO2) was almost identical with the two systems. The differences in arterial P_CO2 and P_O2 between SV-900 and HFPPV were negligible when 30% O₂ was used. The total peripheral resistance (TPR) was lower during ventilation with HFPPV, and although the cardiac output (CO) and stroke volume (SV) were greater during HFPPV, calculations of the tension-time index (TTI) revealed no differences between the two ventilator systems. With 30% O₂ the alveolo-arterial P_O2 difference (A-aD_O2) was smaller, the oxygen flux (OF) greater and the venous admixture lower during ventilation with HFPPV.
The lower TPR during ventilation with HFPPV in association with a higher cardiac output and improved tissue perfusion indicates that the ventilatory pattern in volume-controlled HFPPV interferes less with the cardiovascular functions. Thus, HFPPV appears able to give better myocardial and circulatory efficiency.     

Central Haemodynamics and Oxygen Transport With and Without Continuous Positive Pressure Ventilation After Open-heart Surgery

Twelve patients, subjected 20 h earlier to coronary artery bypass surgery, were studied on discontinuation of the postoperative mechanical ventilation employing PEEP+5 cmH₂O (CMV + PEEP). Compared to the values obtained during CMV + PEEP, cardiac index and mixed venous blood oxygen tension increased with the change to spontaneous ventilation at ambient pressure, employing a 28% O² Ventimask® for the intubated patient. There was a slight decrease in both the arterial oxygen content and oxygen tension, but the increase in cardiac output compensated well for the lowering in the arterial oxygen content, and consequently the systemic oxygen transport was statistically unaltered. Oxygen consumption, pulmonary shunt fraction and arteriovenous oxygen content difference also remained unaltered. The observations suggest that after open-heart surgery, CMV using a PEEP as low as+ 5 cmH₂O may exert, in comparison to controlled oxygen therapy during spontaneous breathing, a significant lowering effect on the already compromised cardiac performance. This necessitates continuous weighing of the beneficial effects obtained by employing postoperative CMV + PEEP, against the adverse haemodynamic effects, although the alterations in cardiac output may partly ensue from the changes in metabolism, muscular effort and oxygen consumption during the two modes of ventilation, although there was no significant increase in oxygen consumption.     

Effects of the Level of CPAP on Central Haemodynamics and Oxygen Transport

The effects of different levels of continuous positive airway pressure (CPAP) on central haemodynamics and oxygen transport were studied in ten spontaneously breathing male patients who had undergone aortocoronary bypass graft operation 18 h earlier. With increasing CPAP levels ranging from 5 cm H₂O (0.49 kPa) (CPAP 5) to 15 cmH₂O (1.47 kPa) (CPAP 15), the cardiac index was found to decrease significantly, while the intraluminal pulmonary capillary wedge and right atrial pressures increased simultaneously. The mean systemic arterial pressure remained unaltered, while the mean pulmonary arterial pressure increased with increasing CPAP. Systemic oxygen transport changed concomitantly with the changes in cardiac output, since arterial blood oxygen content was not altered. The mixed venous blood oxygen tension decreased with increasing CPAP, as did the cardiac output. No changes in the total oxygen consumption or in the arteriovenous oxygen content difference were found at the various CPAP levels. Pulmonary vascular resistance was significantly higher during CPAP 0 than during CPAP 5, possibly indicating development of local pulmonary vasoconstriction following hypoxia caused by closure of the small airways as a consequence of a reduction in the functional residual capacity during CPAP 0. Thus, low level CPAP might be beneficial in maintaining proper lung volume in an intubated patient after aortocoronary bypass surgery. The observations also suggest that, in these patients, CPAP levels exceeding 10 cmH₂O bring about cardiac depression leading to an undesirable reduction in systemic oxygen transport. Mixed venous blood oxygen tension may offer information useful in the adjustment of the level of CPAP.