Influence of dopamine on the pulmonary pressure and shunt volume after cardiac surgery (author's transl)

After the administration of Dopamine to 20 patients after cardiac surgery pulmonary shunt volume was determined with regard to the cardiac output and pulmonary pressure. It was shown that the infusion of Dopamine leads to decrease of the arterio-venous oxygen difference (AVDO2) as well as to the decrease of the PO2 in the arterial blood. On the contrary, in venous bood, PO2, Oxygen saturation, content and pulmonary pressure increased. The increase of the pulmonary right-to-left shunt observed (Qs Qt form 14.9 to 19.2%) is in proportion with the increase in cardiac output. Hence we do not suppose a specific shunting effect of Dopamine. Our findings suggest, that in the case of an already reduced blood oxygen level a further fall of the arterial oxygen saturation caused by a shunt must be avoided by additional enrichment of oxygen content of the inspired air.     

Evaluation of a pulsatile pediatric ventricular assist device in an acute right heart failure model

BACKGROUND: The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume = 9 mL) in a neonatal lamb model of acute right ventricular failure. METHODS: Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n = 5) had no mechanical support whereas experimental group 2 (n = 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery. RESULTS: All results are expressed as mean +/- standard deviation and analyzed by Student's t test. A p value less than 0.05 was considered statistically significant. Base-line measurements were not significantly different between groups and included systemic arterial pressure, 80.6 +/- 12.7 mm Hg; right atrial pressure, 4.6 +/- 1.6 mm Hg; mean pulmonary arterial pressure, 15.6 +/- 4.2 mm Hg; left atrial pressure, 4.8 +/- 0.8 mm Hg; and cardiac output, 1.4 +/- 0.2 L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, 38.8 +/- 10.4 mm Hg; right atrial pressure, 16.8 +/- 2.3 mm Hg; left atrial pressure, 1.4 +/- 0.5 mm Hg; and cardiac output, 0.6 +/- 0.1 L/min. All group 1 animals died at a mean of 71.4 +/- 9.4 minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, 68.0 +/- 13.0 mm Hg; right atrial pressure, 8.2 +/- 2.3 mm Hg; left atrial pressure, 6.4 +/- 2.1 mm Hg; and cardiac output, 1.0 +/- 0.2 L/min. CONCLUSIONS: The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates.     

Preload and incident angle independent index of left ventricular contractility determined by continuous wave Doppler echocardiography

BACKGROUND: Incubating blood with phosphoenolpyruvate decreases hemoglobin oxygen affinity (HOA). This study compared transfusion with phosphoenolpyruvate-treated blood and conventionally stored blood on oxygen consumption in acutely anemic dogs. METHODS: Dogs underwent isovolemic hemodilution (hematocrit = 10%). After 1 hour they were transfused to a hematocrit of 18% with control or phosphoenolpyruvate treated blood. Cardiac output, co-oxymetry, and hemoglobin P50 measurements allowed calculation of oxygen consumption during anemia, and posttransfusion. RESULTS: Hemodilution doubled cardiac output. Transfusion with phosphoenolpyruvate-treated blood allowed greater O2 consumption than control (8.31+/-2.1 and 3.73+/-0.11 cc/kg/mm). There were no differences in arterial or venous PO2 or pH; there were marked differences in HOA, measured by posttransfusion P50 (21+/-3 versus 47+/-4), and mixed venous O2 saturation. CONCLUSIONS: Decreased HOA results in increased O2 consumption in dogs subjected to anemic hypoxia. Phosphoenolpyruvate-treated blood provides increased oxygen consumption at a similar hematocrit when compared with untreated banked blood.     

An intracorporeal (abdominal) left ventricular assist device. Initial clinical trials

We have initiated clinical trials with an intracorporeal (abdominal) partial artificial heart and ten preterminal postcardiotomy patients have been studied. During profound left ventricular failure, the device captures the entire cardiac output from the apex of the left ventricle at low pressures (20 to 40 mm Hg) and ejects (at 80 to 150 mm Hg) into the infrarenal abdominal aorta; the biological aortic valve opens only intermittently and the entire systemic circulation is pump generated. The device is six to ten times more effective than intra-aortic balloon pumping in man and has maintained systemic perfusion during clinical asystole and ventricular fibrillation. We have documented that the profoundly depressed postcardiotomy left ventricle, initially incapable of ejection, can recover during total left ventricular unloading with the abdominal left ventricular assist device support over a seven-day period.     

O2 extraction maintains O2 uptake during submaximal exercise with beta-adrenergic blockade at 4,300 m

Whole body O2 uptake (VO2) during maximal and submaximal exercise has been shown to be preserved in the setting of beta-adrenergic blockade at high altitude, despite marked reductions in heart rate during exercise. An increase in stroke volume at high altitude has been suggested as the mechanism that preserves systemic O2 delivery (blood flow x arterial O2 content) and thereby maintains VO2 at sea-level values. To test this hypothesis, we studied the effects of nonselective beta-adrenergic blockade on submaximal exercise performance in 11 normal men (26 +/- 1 yr) at sea level and on arrival and after 21 days at 4,300 m. Six subjects received propranolol (240 mg/day), and five subjects received placebo. At sea level, during submaximal exercise, cardiac output and O2 delivery were significantly lower in propranolol- than in placebo-treated subjects. Increases in stroke volume and O2 extraction were responsible for the maintenance of VO2. At 4,300 m, beta-adrenergic blockade had no significant effect on VO2, ventilation, alveolar PO2, and arterial blood gases during submaximal exercise. Despite increases in stroke volume, cardiac output and thereby O2 delivery were still reduced in propranolol-treated subjects compared with subjects treated with placebo. Further reductions in already low levels of mixed venous O2 saturation were responsible for the maintenance of VO2 on arrival and after 21 days at 4,300 m in propranolol-treated subjects. Despite similar workloads and VO2, propranolol-treated subjects exercised at greater perceived intensity than subjects given placebo at 4,300 m. The values for mixed venous O2 saturation during submaximal exercise in propranolol-treated subjects at 4,300 m approached those reported at simulated altitudes >8,000 m. Thus beta-adrenergic blockade at 4,300 m results in significant reduction in O2 delivery during submaximal exercise due to incomplete compensation by stroke volume for the reduction in exercise heart rate. Total body VO2 is maintained at a constant level by an interaction between mixed venous O2 saturation, the arterial O2-carrying capacity, and hemodynamics during exercise with acute and chronic hypoxia.     

Right ventricular overload causes the decrease in cardiac output after nitric oxide synthesis inhibition in endotoxemia

OBJECTIVE: To determine whether the decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased left ventricular afterload or right ventricular afterload. DESIGN: Prospective, randomized, unblinded study. SETTING: Research laboratory at an academic, university medical center. SUBJECTS: Nonanesthetized, sedated, mechanically ventilated pigs. INTERVENTIONS: Pigs were infused with 250 microg/kg of endotoxin over 30 mins. Normal saline was infused to maintain pulmonary artery occlusion pressure (PAOP) at a value not exceeding 1.5 times the baseline value. Left ventricular dimensions and function were studied using echocardiography. Right ventricular volumes and ejection fraction were determined via a rapid thermistor pulmonary artery catheter. We also measured mean arterial pressure (MAP), cardiac output, pulmonary arterial pressure, and calculated pulmonary and systemic resistances. Gastric tonometry was used as an index of gastric mucosal oxygenation and peripheral oxygenation. When MAP had decreased to < or =60 mm Hg or had decreased 30 mm Hg from baseline, nine animals received NG-nitro-L-arginine methyl ester (L-NAME) at 15 mg/kg to restore MAP to baseline. A second group of animals (n = 6) continued to receive normal saline, ensuring that PAOP did not exceed 1.5 times its baseline value. A third group of pigs (n = 5) did not receive endotoxin and served as the time control. In this group, a balloon was used to occlude the descending thoracic aorta and to increase MAP by approximately the same amount as in the L-NAME group. MEASUREMENTS AND MAIN RESULTS: Endotoxin caused an increase in pulmonary arterial pressure and right ventricular volumes, and a decrease in gastric mucosal pH. Cardiac output was maintained in the animals receiving the saline infusion. By 2 hrs, pulmonary arterial pressure had decreased but was still notably higher than baseline. However, by this time, MAP had decreased to < or =60 mm Hg. L-NAME administration restored MAP to its baseline value but resulted in worsening pulmonary hypertension, increased right ventricular volumes, and decreased cardiac output, compared with the saline group. Three animals that received L-NAME died of right ventricular failure. We did not observe any evidence of left ventricular dysfunction with increased left ventricular afterload. Moreover, the restoration of MAP with L-NAME infusion did not correct gastric mucosal acidosis. No changes were noted in the time-control group. Occlusion of the thoracic aorta increased MAP but did not change cardiac output. This finding demonstrates that increases in left ventricular afterload of the magnitude seen with the infusion of L-NAME do not lead to decreases in cardiac output. CONCLUSION: The decrease in cardiac output after nitric oxide synthase inhibition in endotoxemia is due to increased right ventricular afterload and not to left ventricular afterload.     

Influence of inhaled nitric oxide on systemic flow and ventricular filling pressure in patients receiving mechanical circulatory assistance

BACKGROUND: In patients with left ventricular (LV) dysfunction, inhaled nitric oxide (NO) decreases pulmonary vascular resistance (PVR) but causes a potentially clinically significant increase in left atrial pressure (LAP). This has led to the suggestion that inhaled NO may reach the coronary circulation and have a negative inotropic effect. This study tested an alternative hypothesis that LAP increases because of volume shifts to the pulmonary venous compartment caused by NO-induced selective pulmonary vasodilation. METHODS AND RESULTS: The Thermo Cardiosystems Heartmate is an LV assist device (LVAD) that can be set (by controlling pump rate) to deliver fixed or variable systemic blood flow. Eight patients (between 1 and 11 days after LVAD implantation) were administered inhaled NO (20 and 40 ppm for 10 minutes), and LAP, systemic flow, and pulmonary arterial pressure were measured in both fixed and variable pump flow modes. In both modes, inhaled NO lowered PVR (by 25 +/- 6% in the fixed mode, P < .001, and by 21 +/- 5% in the variable mode, P < .003). With fixed pump flow, LAP rose from 12.5 +/- 1.2 to 15.1 +/- 1.4 mm Hg (P < .008). In the variable flow mode, LAP did not increase and the assist device output rose from 5.3 +/- 0.3 to 5.7 +/- 0.3 L/min (P < .008). CONCLUSIONS: A selective reduction in PVR by inhaled NO can increase LAP if systemic flow cannot increase. These data support the hypothesis that with LV failure, inhaled NO increases LAP by increasing pulmonary venous volume and demonstrate that inhaled NO has beneficial hemodynamic effects in LVAD patients.     

Effects of endoscopic variceal ligation on oxygen transport and the arterial lactate levels in patients with cirrhosis

OBJECTIVE: Despite the increased cardiac output and oxygen delivery, an impaired oxygen uptake has been noted in patients with cirrhosis. We recently observed that endoscopic variceal ligation decreased the cardiac output due to a reduction in the cardiac preload. It is thus possible that a variceal ligation decreases the oxygen delivery and thereby negatively influences tissue oxygenation in patients receiving such treatment. We thus investigated the effects of variceal ligation on oxygen delivery, oxygen uptake, and the arterial lactate levels. METHODS: There were 22 patients with compensated cirrhosis and risky esophageal varices (Child's class A:B=13:9). Twelve patients underwent an endoscopic variceal ligation and 10 patients received gastroscopy as a control. The cardiac function, blood gas status, oxygen delivery, and arterial lactate concentration were also assessed before and after variceal ligation. The oxygen uptake was calculated by the Fick equation. RESULTS: Following variceal ligation, there was an immediate decrease in the cardiac output and oxygen delivery. The reduction in oxygen delivery was associated with a slight but significant increase in the arterial lactate concentration. The decreased oxygen delivery was also associated with a concomitant decrease in the oxygen uptake. In the control subjects, gastroscopy did not alter the systemic hemodynamics, arterial oxygen status, or arterial lactate levels. CONCLUSION: We found a significant decrease in the oxygen delivery in patients undergoing an endoscopic variceal ligation. Such deteriorated tissue oxygenation may be serious especially in patients with a low oxygen transport ability such as in patients with variceal hemorrhage with anemia. However, the clinical significance of these changes remains unclear and further studies are therefore warranted.     

Detecting gastrointestinal hypoperfusion during cardiac tamponade in pigs: a role for nitric oxide tonometry?

OBJECTIVE: To evaluate different techniques and regional approaches for detecting critical reductions in gastrointestinal (GI) perfusion. DESIGN: Laboratory, animal, controlled study. SETTING: University animal research laboratory. SUBJECTS: Thirteen anesthetized, ventilated, juvenile domestic pigs. INTERVENTIONS: Dextran was infused into the pericardial sac to achieve cardiac tamponade that reduced cardiac output to 25% of baseline value. Hemodynamics were invasively monitored, and blood gases were sampled in the systemic and portal circulations. Tonometers were placed in the corpus of the stomach and in the jejunum, 50 cm aboral to the ligament of Treitz. MEASUREMENTS AND MAIN RESULTS: We measured cardiac output, portal venous blood flow, mesenteric oxygen delivery and consumption, systemic and portal venous blood gases and acid-base balance, stomach and jejunal transepithelial potential difference, stomach and jejunal intramucosal pH, arterial plasma concentrations of asymmetric dimethylarginine, and jejunal, intraluminal nitric oxide. One hour of cardiac tamponade decreased mesenteric oxygen delivery and consumption in a linear fashion and resulted in mesenteric acidosis, as evidenced by decreases in pH, standard bicarbonate, oxygen saturation, and PO2 and increases in PCO2. The potential difference in the jejunum decreased earlier than in the stomach, whereas stomach intramucosal pH decreased before jejunal intramucosal pH. Intraluminal nitric oxide in the jejunum was markedly reduced soon after cardiac tamponade. This reduction was accompanied by an increase in arterial plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Investigated variables were unchanged in control animals. CONCLUSIONS: Both intramucosal pH and potential difference measurements may be used to detect critical reduction in GI perfusion. Regional and temporal differences may reduce the accuracy of these methods. Jejunal tonometry can yield an early nitric oxide measurement that indicates mesenteric low-flow conditions. Jejunal tonometry also yields quantitative information about this modulator of hemodynamic and mucosal barrier function, information that is relevant to GI failure during shock.     

The cardiovascular pharmacology of the antibiotic ionophore Ro 2-2985 (X537A)

Ro 2-2985 increased mean arterial blood pressure in both the venous bypass preparation and the intact animal; however, total peripheral resistance increased in the venous bypass preparation with a constant cardiac output but decreased in the intact animal with an increase in cardiac output. These observations indicate a drug-related increase in the distensibility of the aorta at the same arterial pressure. In vivo ventricular function curves were shifted to the left indicating enhanced myocardial performance with the translocation of large volumes of blood to the central circulation since total body venous compliance was significantly decreased. Beta adrenergic blocking doses of propranolol blocked the positive inotropic effect of Ro 2-2985 while myocardial depression produced by toxic doses of propranolol was reversed. This observation suggests several mechanisms for the Ro 2-2985 metabolic mediation of myocardial muscle contraction. The cardiovascular effects produced by Ro 2-2985 were accompanied by a marked polycythemia and a decrease in plasma volume without a change in total circulating blood volume, while blood glucose values showed a nonsignificant increase. Ro 2-2985 produced a marked increase in cardiac output. The increase in myocardial performance appears to be complex since myocardial force of contraction, dT/dt, dP/dt:P40 and Vmax were all increased. RO 2-2985 increased coronary flow without an increase in resistance. There were no significant increases in myocardial arteriovenous glucose, lactate, K+, Ca++, Na+ or Cl.     

Determination of heart time volume using the Fick principle in the early postoperative phase after correction of congenital heart defects. Comparison of the calculation of arterio-mixed venous oxygen differences and pulmonary oxygen uptake with the calculation of arterial-central venous oxygen differences and pulmonary oxygen uptake

Comparison of the calculation by means of the arterio-mixed venous oxygen difference and the oxygen uptake with the calculation by means of the arterio-central venous oxygen difference and the oxygen uptake. OBJECTIVE: How reliable is the measurement of cardiac output on Fick's principle without a pulmonary artery catheter? SETTING: PICU in an University hospital. DESIGN: In the postoperative period following complete repair of congenital heart disease we carried out 91 simultaneous measurements of blood gases in 45 infants and children (mean age 18.6 months, mean body weight 8.9 kg) from a systemic artery, the A. pulmonalis, and the V. cava superior. We also determined the pulmonary oxygen uptake in 24 patients (48 measurements). Cardiac output was calculated on Fick's principle using the arterio-mixed venous oxygen difference and the pulmonary oxygen uptake (HZV a-pa) and compared to the cardiac output derived from the central venous values (HZV a-zv). We differentiated between patients with a left to right shunt of 10% or more postoperatively (group A, n = 18) and all others (group B, n = 27). RESULTS: In both groups the correlation coefficient between HZV a-zv and HZV a-pa was high (group A: r = 0.97, group B: r = 0.94). In group A HZV a-pa (mean: 1958 ml/min) was higher than HZV a-zv (mean: 1340 ml/min), group B showed the opposite situation (mean HZV a-pa: 1136 ml/min, mean HZV a-zv: 1373 ml/min). With the Wilcoxon signet-rank test we found significant differences between the partial pressure of oxygen and the saturation of central venous and mixed venous blood samples in both groups, but HZV a-zv and HZV a-pa were different significantly on a level of p < or = 0.01 only in group A. CONCLUSIONS: In both groups HZV a-pa and HZV a-zv correlated well. Therefore, if a pulmonary artery catheter is not inserted; the course of the cardiac output can be calculated with acceptable reliability from the central venous blood gases. By means of Fick's principle the pulmonary blood flow is determined, which is higher than the systemic blood flow in cases of left to right shunting, because of the recirculation in the pulmonary blood circuit. Interpreting the results this has to be taken into account.     

Reductions in cardiac output in hypoxic young pigs: systemic and regional perfusion and oxygen metabolism

We tested the hypotheses that, in hypoxic young pigs, reductions in cardiac output restrict systemic oxygen transport to a greater extent than does hypoxia alone and that compensatory responses to this restriction are more effective in higher than in lower priority vasculatures. To study this, 10- to 14-day-old instrumented awake hypoxic (arterial oxygen tension = 39 Torr) pigs were exposed to reduced venous return by inflation of a right atrial balloon-tipped catheter. Blood flow was measured with radionuclide-labeled microspheres, and oxygen metabolism was determined with arterial and venous oxygen contents from appropriate vessels. Hypoxia resulted in a reduction in oxygen tension; increases in cardiac output and perfusion to brain (72% over baseline), heart, adrenal glands, and liver without reductions to other organs except for the spleen; reductions in systemic and intestinal oxygen delivery; and increases in systemic and intestinal oxygen extraction without changes in systemic, cerebral, or intestinal oxygen uptake. During hypoxia, decreasing venous return was associated with increases in arterial lactic acid concentration and central venous pressure; attenuation of the hypoxia-related increase in cardiac output; sustained increases in brain (72% over baseline) and heart perfusion; reductions in lung (bronchial artery), pancreatic, renal, splenic, and intestinal (-50% below baseline) perfusion; decreases in systemic and gastrointestinal oxygen delivery; sustained increases in systemic and intestinal oxygen extraction; and decreases in intestinal oxygen uptake, without changes in cerebral oxygen metabolism. We conclude that when venous return to the heart is reduced in hypoxic young pigs, the hypoxia-related increase in cardiac output was attenuated and the relative reduction in cardiac output was associated with preserved cerebral oxygen uptake and compromised intestinal oxygen uptake. Regional responses to hypoxia combined with relative reductions in cardiac output differ from that of hypoxia alone, with the greatest effects on lower priority organs such as the gastrointestinal tract.     

Induction of ventricular collapse by an axial flow blood pump

An important consideration for clinical application of rotary blood pump based ventricular assist is the avoidance of ventricular collapse due to excessive operating speed. Because healthy animals do not typically demonstrate this phenomenon, it is difficult to evaluate control algorithms for avoiding suction in vivo. An acute hemodynamic study was thus conducted to determine the conditions under which suction could be induced. A 70 kg calf was implanted with an axial flow assist device (Nimbus/UoP IVAS; Nimbus Inc., Rancho Cordova, CA) cannulated from the left ventricular apex to ascending aorta. On initiation of pump operation, several vasoactive interventions were performed to alter preload, afterload, and contractility of the left ventricle. Initially, dobutamine increased contractility and heart rate ([HR] = 139; baseline = 70), but ventricular collapse was not achievable, even at the maximal pump speed of 15,000 rpm. Norepinephrine decreased HR (HR = 60), increased contractility, and increased systemic vascular resistance ([SVR] = 24; baseline = 15), resulting in ventricular collapse at a pump speed of 14,000 rpm. Isoproterenol (beta agonist) increased HR (HR = 103) and decreased SVR (SVR = 12), but ventricular collapse was not achieved. Inferior vena cava occlusion reduced preload, and ventricular collapse was achieved at speeds as low as 11,000 rpm. Esmolol (beta1 antagonist) decreased HR (HR = 55) and contractility, and ventricular collapse was achieved at 11,500 rpm. Episodes of ventricular collapse were characterized initially by the pump output exceeding the venous return and the aortic valve remaining closed throughout the cardiac cycle. If continued, the mitral valve would remain open throughout the cardiac cycle. Using these unique states of the mitral and aortic valves, the onset of ventricular collapse could reliably be identified. It is hoped that the ability to detect the onset of ventricular collapse, rather than the event itself, will assist in the development and the evaluation of control algorithms for rotary ventricular assist devices.     

Early hemodynamic effects of olprinone hydrochloride after coronary artery bypass grafting

Our purpose was to evaluate the hemodynamic effects of olprinone hydrochloride early after coronary artery bypass grafting (CABG). Fifteen patients undergoing CABG were administered a constant infusion of 0.1 microgram/kg/min of olprinone and continued for 4 hours. No bolus infusion of olprinone was administered before continuous infusion. Systolic systemic arterial pressure, systolic pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance were significantly decreased. There were no significant changes in heart rate, mean central venous pressure, mean left atrial pressure and left ventricular stroke work index. Cardiac index was significantly increased, but a correlation between cardiac index and mixed venous blood oxygen saturation was not found. Double product was significantly decreased, which described above suggest that olprinone achieved improvement of left cardiac function without more myocardial oxygen consumption. Severe transient hypotension (systolic arterial pressure < 80 mmHg) after infusion of olprinone was observed in three patients. Olprinone administered soon after CABG surgery had beneficial effects in terms of improvement of hemodynamic status without more oxygen consumption and reduction of pulmonary vascular resistance. However transient hypotension was a serious clinical problem in patients after open heart surgery, especially in CABG patients who need suitable systolic arterial pressure to keep enough blood perfusion of arterial bypass grafts.     

Effects of oxygen, positive end-expiratory pressure, and carbon dioxide on oxygen delivery in an animal model of the univentricular heart

OBJECTIVE: Respiratory manipulations are a mainstay of therapy for infants with a univentricular heart, but until recently little experimental information has been available to guide their use. We used an animal model of a univentricular heart to characterize the physiologic effects of a number of commonly used ventilatory treatments, including altering inspired oxygen tension, adding positive end-expiratory pressure, and adding supplemental carbon dioxide to the ventilator circuit. RESULTS: Lowering inspired oxygen tension decreased the ratio of pulmonary to systemic flow. This ratio was 1.29 +/- 0.08 at an inspired oxygen tension of 100%, 0.61 +/- 0.09 at an inspired oxygen tension of 21%, and 0.42 +/- 0.09 at an inspired oxygen tension of 15% (p < 0.05 compared with an inspired oxygen tension of 100% and a positive end-expiratory pressure of 0 cm H2O). High-concentration supplemental carbon dioxide (carbon dioxide tension of 80 to 90 mm Hg) added to the ventilator circuit decreased inspired oxygen tension from 1.29 +/- 0.11 to 0.42 +/- 0.12 (p < 0.05 compared with baseline). A mixture of 95% oxygen and 5% carbon dioxide (carbon dioxide tension of 50 to 60 mm Hg) did not decrease the pulmonary/systemic flow ratio significantly. All three types of interventions influenced systemic oxygen delivery, which was a function of the pulmonary/systemic flow ratio. As the pulmonary/systemic flow ratio decreased from initially high levels (greater than 1), oxygen delivery first increased and reached an optimum at a flow ratio slightly less than 1. As the pulmonary/systemic flow ratio decreased further, below 0.7, oxygen delivery decreased. The ability of systemic arterial and venous oxygen saturations to predict the pulmonary/systemic flow ratio was examined. Venous oxygen saturation correlated well with both pulmonary/systemic flow ratio and systemic oxygen delivery, whereas arterial oxygen saturation did not accurately predict either pulmonary/systemic flow ratio or oxygen delivery. CONCLUSION: This model demonstrated the value of estimating the pulmonary/systemic flow ratio before initiating therapy. When the initial ratio was greater than about 0.7, interventions that decreased the ratio increased oxygen delivery and were beneficial. When the initial pulmonary/systemic flow ratio was below 0.7, interventions that decreased the ratio decreased oxygen delivery and were detrimental. We conclude by presenting a framework to guide therapy based on the combination of arterial and venous oxygen saturations and the estimate of the pulmonary/systemic flow ratio that they provide.     

Role of calciotrophic hormones in calcium mobilization of lactation

In two consecutive studies (Study A and Study B), we evaluated the effects of increasing doses of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringer's solution, 24 patients (12 in each study) were randomly assigned to receive, within 30 min, a predetermined volume of either HBOC-201 or 6% hydroxyethyl starch (Study A 6.9 mL/kg; Study B 9.2 mL/kg). Monitored variables included systemic and pulmonary arterial pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic (SVRI) and pulmonary (PVRI) vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). In both studies, the infusion of HBOC-201 was associated with increases in SVRI (Study A 121%; Study B 71%) and PVRI (Study A 70%; Study B 53%) and with a decrease in CI (29% both studies). Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch, but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI, with a resulting net decrease in both CI and DO2I (Study A 30%; Study B 28%); VO2I was maintained by increased O2ER. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. Implications: Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch.     

Circulatory support with a left-heart assist device after intracardiac operation: design concepts and management techniques

A simple left-heart assist device was developed to reduce left ventricular preload while simultaneously increasing total systemic blood flow. It consists of special cannulas connected to a simple extracorporeal tubing loop and roller pump, designed to permit bypass of as much as 5 liters of blood per minute from left atrium to ascending aorta. Employed in 15 patients with advanced heart disease who were in low cardiac output following repair, the system was proven effective. An asset of the device is the ability to subsequently separate the patient from the device without need to reenter the thorax or abdomen.     

Direct antagonism of ethanol''s effects on GABA(A) receptors by increased atmospheric pressure

We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glycerol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.     

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

The effect of hypovolemic shock and reperfusion on the hepatic oxygen supply-uptake relationship in the dog

The hepatic oxygen supply-uptake relationship was investigated during hypovolemic shock using a right heart bypass technique. The results were dissimilar to those previously reported in that the ratio of liver oxygen delivery to systemic oxygen delivery was significantly decreased during shock. The decreased ratio was due to a significant decrease in the portal venous oxygen delivery when compared to the decrease in the systemic oxygen delivery. The decrease in portal venous oxygen delivery was caused not only by the decrease in portal venous blood flow, but also by the decrease in oxygen content of portal blood. The ratio of hepatic arterial oxygen delivery, on the other hand, was significantly increased during shock. Hypovolemic shock increased the liver oxygen extraction ratio to nearly 100% of the pre-shock value. These findings suggest a hepatic protective mechanism for matching oxygen uptake to rising hepatic oxygen requirements. Liver oxygen delivery returned to pre-shock value after correction of hypovolemia primarily due to a significant increase in hepatic arterial oxygen delivery. A significant negative correlation between the liver oxygen extraction ratio and the oxygen content of hepatic venous blood was observed. The hepatic venous oxygen content appears to be a simple and appropriate index of liver oxygenation in clinical medicine because it is difficult to evaluate the liver oxygen extraction ratio directly.