Measurement Of Hemodynamic Parameters Research Articles

Intraoperative monitoring for safety of bilateral total knee replacement.

Cardiopulmonary hemodynamics in 79 consecutive patients who had one-stage bilateral total knee replacements were monitored prospectively with a pulmonary artery catheter. The pulmonary vascular resistance, wedge pressure, pulmonary artery pressure, and systemic vascular resistance were measured before skin incision, 5 to 10 minutes after implanting the first total knee replacement, and after the second knee replacement. The second knee replacement was cancelled in five patients because the pulmonary vascular resistance after the first knee replacement was more than double the baseline, or above 200 dyne/second/cm(5). No patient had clinical symptoms of fat embolism during the postoperative course. Patient predictive factors, or the use of pulse oximetry readings instead of a pulmonary artery catheter, were not predictive of intraoperative elevation of pulmonary vascular resistance. For this reason, the safety of this operation for the patient requires that intraoperative measurement of hemodynamic parameters of embolism be done.

Naloxone Improves Splanchnic Perfusion in Conscious Dogs through Effects on the Central Nervous System

In patients undergoing colonoscopy, naloxone has vasodilative properties. However, it remains unclear whether this effect is mediated by central or peripheral mechanisms. The aim of this study was to investigate whether these effects are mediated by an effect of naloxone on the central nervous system. Twenty dogs were chronically instrumented for measurement of hemodynamic parameters. Splanchnic blood flow was determined using colored microspheres. Transthoracic echocardiographic examinations were performed to measure cardiac output. In each animal, two experiments were performed in a random order: experiment 1 was determination of splanchnic blood flow before and 5 min after intravenous administration of naloxone (63 microg/kg), and experiment 2 was determination of splanchnic blood flow before and 5 min after administration of naloxone methiodide (63 microg/kg), which does not cross the blood-brain barrier. Naloxone, but not naloxone methiodide, significantly increased blood flow to the stomach (from 0.41 +/- 0.022 to 0.9 +/- 0.016# ml x g (-1) x min(-1) with naloxone), jejunum (from 0.31 +/- 0.024 to 0.83 +/- 0.083# ml x g(-1) x min(-1) with naloxone), colon (from 0.41 +/- 0.057 to 0.68 +/- 0.008# ml x g(-1) x min(-1) with naloxone), spleen (from 1.45 +/- 0.21 to 2.13 +/- 0.25# ml x g(-1) x min(-1) with naloxone), pancreas (from 0.97 +/- 0.021 to 1.25 +/- 0.005# ml x g(-1) x min(-1) with naloxone), and kidneys (from 3.24 +/- 0.108 to 5.31 +/- 0.26# ml x g(-1) x min(-1) with naloxone), without altering cardiac output or arterial blood pressure in conscious dogs. There were no differences in the hemodynamics or cardiac output between the two experiments. Data are presented as mean +/- SD. The increased splanchnic perfusion after naloxone is not caused by direct peripheral vascular effects or increased cardiac output. Indirect vasodilative effects on splanchnic vessels mediated by actions of naloxone on the central nervous system account for the increased gastrointestinal perfusion after naloxone in dogs.

Evaluation of left ventricular volumes and ejection fraction with a nonfluoroscopic endoventricular three-dimensional mapping technique

Background Recently, a novel nonfluoroscopic 3-dimensional electromechanical mapping technique was introduced in the clinical arena. Although initial in vitro and in vivo studies suggested the reliability of the system in volumetric and hemodynamic evaluation of the left ventricle, no validation in human beings has been performed. Methods A nonfluoroscopic electromechanical mapping (NOGA, Biosense-Webster) procedure was performed in 44 patients. All patients received a contrast left ventriculogram during the same session. Volumetric (end-diastolic [EDV] and end-systolic volumes [ESV]) and hemodynamic (left ventricular ejection fraction [LVEF] and stroke volume) parameters of both systems were compared. Results Two uncomplicated pericardial effusions occurred with the first-generation mapping catheters. No procedural complications were noted with the new-generation mapping catheters. Significant correlations were found between mapping-derived and ventriculography-based measurements for both ESV (r = 0.67, P < .001) and LVEF (r = 0.78, P < .001). Absolute volumes, however, were only comparable for ESV (46.6 ± 25.3 mL vs 48.8 ± 37.0 mL, respectively; P = .13) but differed greatly for LVEF (35% ± 13% vs 65% ± 19%, respectively; P < .001), EDV (69.1 ± 28.6 mL vs 125.9 ± 53.4 mL, respectively; P < .001) and stroke volume (22.4 ± 9.9 mL vs 77.1 ± 33.7 respirations; P < .001). Moreover, Bland-Altman analysis showed the clinical noninterchangeability between these techniques for the measurement of hemodynamic parameters. Conclusion Measurement of hemodynamic parameters with nonfluoroscopic mapping of the left ventricle is feasible and safe. The system provides data that strongly correlate but that are in clinical disagreement with angiographic data. Therefore the interchangeability of these techniques may be questioned. (Am Heart J 2000;140:596-602.)

STUDY OF CAVERNOSAL ARTERIAL ANATOMY USING COLOR AND POWER DOPPLER SONOGRAPHY: IMPACT ON HEMODYNAMIC PARAMETER MEASUREMENT

Purpose We report on color and power Doppler ultrasound to study cavernosal arterial anatomy, and evaluate the impact of vascular anatomy on the measurement of hemodynamic parameters. Materials and Methods Cavernosal arterial anatomy of 42 patients with erectile dysfunction was evaluated using color and power Doppler ultrasound. A computerized waveform analysis was used to measure peak systolic velocity, end diastolic velocity and resistive indexes at various sites, including the penile crura, and proximal mid and distal penile shaft. Hemodynamic parameters were measured in each artery in cases of bifurcated or multiple cavernosal arteries. Results A total of 80 corpora were adequately evaluated. We observed a single artery without major proximal branches in 37 corpora, a single artery with major proximal branches in 17, bifurcated arteries in 15, 2 cavernosal arteries in 4 and marked arterial tortuosity in 1. In 6 corpora the main cavernosal artery arose from the superficial dorsal artery. The peak systolic velocity was highest at the proximal and decreased progressively at the distal site. The peak systolic velocity plus or minus standard deviation at the mid shaft averaged 69.3 +/- 30.0% of that at the proximal penile shaft. Of the 15 corpora with bifurcated arteries 67% had a 40% or greater difference in peak systolic velocity between the branches. Complete or partial occlusion of the cavernosal artery was identified in 3 corpora, and a dramatic difference in peak systolic velocity proximal and distal to the stenotic area was demonstrated. Conclusions Cavernosal arterial anatomy is variable and hemodynamic parameters differ at various sites of measurement. Parameters should be measured at a consistent proximal site to obtain a reliable assessment. Variations in vascular anatomy and cavernosal artery pathology should be considered when interpreting color Doppler sonography and before penile vascular surgery.

Contribution of non-cardiomyocyte apoptosis to cardiac remodelling that occurs in the transition from compensated hypertrophy to heart failure in spontaneously hypertensive rats

Various alterations in molecular and cellular events have been considered as possibly contributing to the cardiac remodelling that occurs during the transition from compensated hypertrophy to heart failure. The aim of the present study is to clarify (1) whether cardiac apoptosis occurs during the transition from compensated hypertrophy to decompensated heart failure, and (2) whether expression of the genes encoding Bax (an apoptosis inducer) and Bcl-xL and Bcl-2 (apoptosis inhibitors) is altered during this transition. We used 12-month-old and 20-month-old male spontaneously hypertensive rats (SHR(12) and SHR(20) respectively) and age-matched Wistar-Kyoto rats (WKY(12) and WKY(20) respectively). These rats were killed after measurement of haemodynamic parameters by transthoracic echocardiography and use of a tipmanometer via the right carotid artery. The expression of bcl-2, bcl-xL and bax was analysed by Northern blotting. Samples were also fixed in 4% paraformaldehyde for in situ nick end-labelling (TUNEL) methods and immunohistochemistry. SHR(12) had well compensated left ventricular hypertrophy with normal fractional shortening and normal end-systolic wall stress. In contrast, the hearts of SHR(20) developed decompensated dilatation, with a decrease in fractional shortening and an increase in end-systolic wall stress. TUNEL-positive cells were seen exclusively in the hearts of SHR(20). The major cell types that showed TUNEL-positive nuclei were non-cardiomyocytes. The expression of bax remained unchanged during the transition to heart failure. However, there was increased expression of bcl-xL in the failing stage, whereas the expression of bcl-2 remained unchanged. Immunohistochemical studies revealed that Bcl-xL protein was up-regulated in the hearts of SHR(20). In conclusion, non-cardiomyocyte apoptosis may play a contributory role in the remodelling that occurs in the transition from compensatory hypertrophy to decompensated heart failure. In addition, it is suggested that enhanced expression of bcl-xL plays an important role in the preservation of cardiomyocytes during this transition.

4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine.

4-Chloro-m-cresol (4-CmC) induces marked contractures in skeletal muscle specimens from individuals susceptible to malignant hyperthermia (MHS). In contrast, 4-CmC induces only small contractures in specimens from normal (MHN) patients. 4-CmC is a preservative within a large number of commercially available drug-preparations (e.g., insulin, heparin, succinylcholine), and it has been suggested that 4-CmC might trigger malignant hyperthermia. This study was designed to investigate the effects of 4-CmC in vivo and in vitro in the same animals. After approval of the animal care committee, six Pietrain MHS and six control (MHN) swine were anesthetized with azaperone 4 mg/kg intramuscularly and metomidate 10 mg/kg intraperitoneally. After endotracheal intubation, lungs were mechanically ventilated (inspired oxygen fraction 0.3) and anesthesia was maintained with etomidate 2.5 mg x kg(-1) x h(-1) and fentanyl 50 microg x kg(-1) x h(-1). Animals were surgically prepared with arterial and central venous catheters for measurement of hemodynamic parameters and to obtain blood samples. Before exposure to 4-CmC in vivo, muscle specimens were excised for in vitro contracture tests with 4-CmC in concentrations of 75 and 200 microM. Subsequently, pigs were exposed to cumulative administration of 3, 6, 12, 24, and 48 mg/kg 4-CmC intravenously. If an unequivocal episode of malignant hyperthermia occurred, as indicated by venous carbon dioxide concentration > or = 70 mmHg, pH < or = 7.25, and an increase of temperature > or = 2 degrees C, the animals were treated with dantrolene, 3.5 mg/kg. All MHS swine developed malignant hyperthermia after administration of 4-CmC in doses of 12 or 24 mg/kg. Venous carbon dioxide concentration significantly increased and pH significantly decreased. Temperature increased in all MHS animals more than 2 degrees C. Blood lactate concentrations and creatine kinase levels were significantly elevated. All MHS swine were treated successfully with dantrolene. In contrast, no MHN swine developed signs of malignant hyperthermia. After receiving 4-CmC in a concentration of 48 mg/kg, however, all MHN animals died by ventricular fibrillation. The in vitro experiments showed that both concentrations of 4-CmC produced significantly greater contractures in MHS than in MHN specimens. 4-CmC is in vivo a trigger of malignant hyperthermia in swine. However, the 4-CmC doses required for induction of malignant hyperthermia were between 12 and 24 mg/kg, which is about 150-fold higher than the 4-CmC concentrations within clinically used preparations.

Non-invasive in vivo mapping of tumour vascular and interstitial volume fractions.

Non-invasive measurement of haemodynamic parameters and imaging of neovasculature architecture is of importance in determining tumour prognosis, in directing tissue sampling and in assessing treatment efficacy. In the current research we investigated a dual tracer nuclear magnetic resonance (NMR) technique to map the tumour vascular (VVF) and interstitial volume fraction (IVF) non-invasively in vivo. We hypothesised that a NMR signal emanating after intravenous administrations of a vascular paramagnetic probe (MPEG-PL-GdDTPA) can be maximised so that additional signal after administration of a second interstitial probe (GdDTPA) would only reflect the IVF but not the VVF. The method and its assumptions were verified and experimental conditions optimised both in phantoms and in C6 glioma bearing rats. Data derived from in vivo studies show tumoral VVF and IVF values that are consistent with histology data and literature values; the relative ranking order of values was tumour > muscle > brain. Image maps showed intratumoral and intertumoral heterogeneity of both parameters at submillimetre pixel resolution. The method is applicable to a wide variety of tumour models and can theoretically be performed repeatedly to study tumour growth or involution during therapy.

Bovine hemoglobin. HBOC-201 causes a reduction of the oxygen partial pressure in poststenotic skeletal muscle

We investigated the effects of ultrapurified polymerized bovine hemoglobin (HBOC-201) on skeletal muscle tissue oxygen tension when applied before establishment of a nearly complete arterial stenosis. Twelve foxhounds were anaesthetized IV and mechanically ventilated with 30% oxygen in air. Catheters were inserted into the right femoral artery and vein for measurements of haemodynamic parameters and blood-gas sampling. Arterial blood flow of the left popliteal artery was measured by an electromagnetic flow probe. Skeletal muscle tissue oxygen tension (tpo2) was measured in the left gastrocnemic muscle using a stepwise-driven polarographic needle probe, creating histograms from 200 single tpO2 measurements. Following isovolaemic haemodilution with Ringer's solution to a target haematocrit of 20%, the animals were randomly assigned to receive either 200 ml of predonated fresh blood (group 1) or 200 ml of HBOC-201 (MW 32,000-500,000; Hb 13 +/- 1 g-dl-1, group 2). After a 15-min stabilization period, a 95% artificial stenosis of the left popliteal artery was established. While animals of group 1 received two applications of 200 ml 6% hetastarch (HES, 200,000; 0.5), animals of group 2 received 200 ml Ringer's solution 45 and 75 min after establishment of the arterial stenosis, respectively. Variables were measured at baseline, after haemodilution and application of the respective compound, and 30, 60 and 90 min after establishment of the stenosis. Demographic data, muscle temperature and arterial blood gases did not differ between groups. With the exception of a higher mean pulmonary artery pressure in HBOC-201-treated animals, haemodynamics did not differ between groups. In both groups oxygen delivery and oxygen consumption of the muscle decreased in parallel to the decreasing blood flow during arterial stenosis. In contrast, oxygen extraction ratio increased after infusion of HBOC-201 and remained unchanged during stenosis (P < 0.05). In group 1, the tpO2 decreased during stenosis when compared to baseline (P < 0.001) and remained decreased after administration of HES. In contrast, administration of 200 ml of HBOC-201 before establishment of the arterial stenosis sustained the tpO2 values at nearly baseline levels during stenosis. Skeletal muscle tissue oxygen tension was higher after HBOC-201 infusion during stenosis when compared to HES infusion (P < 0.001). These data suggest that haemoglobin solutions can reach poststenotic tissues. The increased oxygen extraction after application of HBOC-201 is associated with improved skeletal muscle oxygen tension during severe arterial stenosis.

Modeling hemodynamic response for analysis of functional MRI time-series.

The standard Gaussian function is proposed for the hemodynamic modulation function (HDMF) of functional magnetic resonance imaging (fMRI) time-series. Unlike previously proposed parametric models, the Gaussian model accounts independently for the delay and dispersion of the hemodynamic responses and provides a more flexible and mathematically convenient model. A suboptimal noniterative scheme to estimate the hemodynamic parameters is presented. The ability of the Gaussian function to represent the HDMF of brain activation is compared with Poisson and Gamma models. The proposed model seems valid because the lag and dispersion values of hemodynamic responses rendered by the Gaussian model are in the ranges of their previously reported values in recent optical and fMR imaging studies. An extension of multiple regression analysis to incorporate the HDMF is presented. The detected activity patterns exhibit improvements with hemodynamic correction. The proposed model and efficient parameter estimation scheme facilitated the investigation of variability of hemodynamic parameters of human brain activation. The hemodynamic parameters estimated over different brain regions and across different stimuli showed significant differences. Measurement of hemodynamic parameters over the brain during sensory or cognitive stimulation may reveal vital information on physiological events accompanying neuronal activation and functional variability of the human brain, and should lead to the investigation of more accurate and complex models.

EFFECTS OF CARDIOTROPHIN-1 ON HAEMODYNAMICS AND CARDIAC FUNCTION IN CONSCIOUS RATS

Cardiotrophin-1 (CT-1), a newly discovered cytokine, has been shown to induce cardiac hypertrophy in vitro and in vivo. The present study examined the effects of CT-1 on haemodynamics and cardiac function. The measurements of haemodynamic parameters were made using in-dwelling catheters and flow probes in conscious, unrestrained rats. Intravenous administration of CT-1 caused a dose-dependent decrease in mean arterial pressure (MAP), and an increase in heart rate (HR). CT-1 (100 μg/kg) significantly elevated cardiac output and HR, and decreased MAP and systemic vascular resistance. Stroke volume was unaltered, suggesting that the CT-1 induced increase in cardiac output was secondary to increased HR. There was no significant difference in left ventricular maximal dP/dtbetween the CT-1-treated and vehicle-treated groups, suggesting that CT-1 might not induce a meaningful change in ventricular contractility. Pretreatment with intravenous Nω-nitro-l-arginine methyl ester, a specific inhibitor of nitric oxide synthase, significantly attenuated the depressor and tachycardic responses to CT-1. These results indicate that nitric oxide plays an important role in mediating the haemodynamic effects of CT-1.

Is Hyperbaric Oxygen More Effective than Carbogen/Nicotinamide in Tumor Radiation Response?

radiosensitizers. They demonstrated tumor growth delay to be significantly longer after irradiation combined with hyperbaric oxygen ? nicotinamide than in combination with carbogen + nicotinamide. In the last decades, different methods to overcome tumor hypoxia have been used in the clinic. A meta-analysis (2) demonstrated the efficacy of hyperbaric oxygen in improving local tumor control and overall survival. Both physiological and radiobiological aspects of hyperbaric oxygen were discussed recently (3). One of the conclusions of the workshop was that more experimental data, particularly the comparison of hyperbaric oxygen with other treatment modalities, are warranted. At our institution we are engaged in both experimental (4) and clinical studies (5) with hyperbaric oxygen. We would therefore like to make some remarks. First, we want to discuss the authors' conclusion that hyperbaric oxygen is a more effective radiosensitizer than carbogen, since this is based on data for tumor growth delay after irradiation with large single-dose fractions. In their experiments, tumor vasculature might be damaged by the polarographic pO02 needle as well as by the thermocouple probe insertions, and animals were under anesthesia while being irradiated. Suit et al. (6) demonstrated in a TCD,0 study with hyperbaric oxygen an increase in the oxygen enhancement ratio (OER) from 1.25 without to 2.01 with pentobarbital anesthesia. Measurements of hemodynamic parameters in a previous study do not rule out the possibility that tumor oxygenation and tumor response are influenced by the use of pentobarbital in their model (7). Furthermore, the apparent inefficiency of carbogen for radiosensitizing the R3230Ac carcinoma has to be considered, since in most experimental studies, carbogen breathing alone did result in an increased tumor response (for overview see ref. 8). Randomized clinical trials with adequate preirradiation breathing times and sufficient numbers of patients are lacking. However, a few phase II studies indicate favorable results with carbogen breathing alone (9). The authors suggest that hyperbaric oxygen may improve the radiation response by additional mechanisms of cell killing. Indeed, exposure to hyperbaric oxygen alone was found to increase DNA damage in human leukocytes (10). Interestingly, DNA damage was evident after the first treatment but not after repeated exposures. To our knowledge there are no such data for tumor tissue. It is questionable, however, whether the supposed additional cell-killing effect can be extrapolated to multifraction experiments. Recently, a local control assay was performed with unanesthetized Wag/Rij rats at our institution.' R1H rhabdomyosarcomas transplanted in the flank were irradiated with 30 fractions of 2 Gy of X rays for an overall treatment time of 41 days. Ten animals per group were assigned randomly to treatment in air, normobaric carbogen or high-pressure oxygen (240 kPa). One animal treated in air, two treated in hyperbaric oxygen and four treated in carbogen developed lung metastases (log rank test P = 0.3). Carbogen and hyperbaric oxygen yielded the same local control probability. The local control for both groups was significantly higher compared to the air-breathing control group (Table I). Model calculations presented by Wouters and Brown in this journal (11) showed that tumor response in fractionated studies is highly dependent upon the cells at oxygen levels intermediate (oxygen partial pressure from 0.5 to 20 mm Hg) between the radiobiologically hypoxic and welloxygenated fractions. Figure 2 of their article shows the hypothetical tumor cell survival after single-dose irradiation of a well-oxygenated tumor and of a tumor in which a hypoxic fraction of 20% was assumed. At high doses (>10 Gy),

Hemodynamic monitoring: a comparison of research and practice

Measurement of hemodynamic parameters is a common practice and is well researched, but little information is available on the translation of the research into actual practice. To determine (1) the current practice of hemodynamic measurement in relation to positioning of patients and (2) the barriers to use of research related to hemodynamic monitoring. A stratified, random, national sample of 1000 members of the American Association of Critical-Care Nurses was surveyed by mail about hemodynamic monitoring procedures related to the positioning of patients and beds, technique used to determine the position of the bed, number of measurements of cardiac output, use of iced versus room-temperature injectate, use of printed or digital information, nurses' input into written procedures, and barriers to research utilization. In actual practice, 24.1% of the respondents always keep the bed flat when measuring pulmonary artery pressures, 55.0% elevate the head of the bed 30 degrees or less, 80.7% always have patients supine for measurements, and 13.3% place patients in lateral or other positions. Unit policy dictated the flat position in 25.8% of the sample; nurse managers (41.4%), staff nurses (27.5%), and staff committees (31.2%) were involved in writing the procedure. Respondents viewed research related to hemodynamic monitoring procedures as relevant and valuable. The greatest barriers to utilization were lack of staff support for implementation, insufficient time to implement research findings, and feelings among nurses that they lacked authority to implement change. Research findings are generally being implemented at the bedside, although not completely or consistently. Minimizing the barriers to use of research is within the scope of nurses' practice.

Cardiac secretion of atrial and brain natriuretic peptides in acuteischaemic heart failure in pigs: effect of angiotensin II receptor antagonism

In a model of acute ischaemic left ventricular failure in pigs, we compared the plasma levels and cardiac secretion of the three atrial peptides, atrial natriuretic factor (ANF), N-terminal proatrial natriuretic factor (N-terminal proANF) and brain natriuretic peptide (BNP). Acute ischaemic left ventricular failure was induced by embolization of the left coronary artery with plastic microspheres. Thereafter, treatment was given by an intravenous injection of the angiotensin II receptor (AT1) antagonist losartan. Effects of failure induction and treatment were documented by measurement of haemodynamic parameters and plasma concentrations of catecholamines, plasma renin activity, angiotensin II and aldosterone. Acute left ventricular failure was accompanied by significant increases in cardiac secretion and plasma levels of all three atrial peptides, which was considerably more pronounced for ANF and N-terminal proANF than for BNP. Treatment with losartan resulted in significant decreases in plasma ANF and N-terminal proANF, whereas BNP did not change. These findings indicate that ANF and N-terminal proANF may be better suited than BNP as markers of cardiac preload during the development and treatment of acute heart failure.

Bovine hemoglobin increases skeletal muscle oxygenation during 95% artificial arterial stenosis

Background . This study investigates the effect of a stroma-free ultmpurified bovine hemoglobin solution (HBOC) on skeletal muscle tissue oxygenation in comparison with hetastarch during nearly complete arterial stenosis. Methods . Fourteen foxhounds were intravenously anesthetized and mechanically ventilated with 30% oxygen in air. Catheters were inserted into the right femoral artery and vein for measurements of hemodynamic parameters and blood gas sampling. Arterial blood flow of the left popliteal artery was measured by means of an electromagnetic flow probe. Skeletal muscle tissue oxygen tension (tpO 2) was measured in the left gastrocnemius muscle by using a stepwise driven polarographic needle probe creating histograms from 200 single tpO 2 measurements. After isovolemic hemodilution with Ringer's lactate solution to a hematocrit of 25%, a 95% artificial stenosis of the popliteal artery was established. The animals then randomly received two applications of either 50 ml HBOC (molecular weight, 32,000 to 500,000; hemoglobin, 13 ± 1 gm/dl −1) or 200 ml 6% hetastarch 200,000/0.5. Variables were measured at baseline, after hemodilution, 30 minutes after stenosis, and 15 minutes after two applications of the respective compound. Results . Demographic data, muscle temperature, and arterial blood gases did not differ between groups. With the exception of higher mean arterial and mean pulmonary artery pressures in HBOC-treated animals, hemodynamics did not differ between groups. In both groups oxygen delivery and oxygen consumption of the muscle decreased in parallel to the decreasing blood flow during arterial stenosis. In contrast, oxygen extraction ratio increased after infusion of HBOC and was higher after the second application when compared with hetastarch-treated animals (p < 0.05). During stenosis tpO 2 was decreased in both groups when compared with baseline (p < 0.001). Mean tpO2 remained at decreased levels after administration of hetastarch but increased to nearly baseline values after HBOC treatment (p < 0.001). Conclusions . The data suggest that increased oxygen extraction in the HBOC group is associated with improved skeletal muscle tissue oxygenation during severe arterial stenosis.

Initial experience with an implantable hemodynamic monitor.

Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock: Br J Pharmacol 1995; 114/2: 363–368

1 The present investigation compares the effects of intravenous infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) with that of an inhalation with NO gas in a porcine model of endotoxin (lipopolysaccharide, LPS) shock. In addition, the effects of the combination of these two treatments were also investigated. 2 Male pigs were anaesthetized and instrumented for the measurement of haemodynamic parameters. Blood samples were withdrawn at different time intervals for determination of blood gases, pH, and plasma levels of nitrite/nitrate and tumour necrosis factor. 3 Endotoxin infusion (15 μg kg−1 h−1 for 3 h) caused a progressive fall in mean arterial blood pressure (MABP) and cardiac output (CO) and a biphasic increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistence (PVR). A continuous infusion of l-NMMA (0.1 mg kg−1 min−1) significantly attenuated the fall in MABP, but did not affect MPAP, CO and PVR. NO-inhalation (50 p.p.m.) did not affect MABP, but significantly blunted the biphasic increase in MPAP and PVR and significantly delayed the fall in CO. The combination of l-NMMA infusion (0.1 mg kg−1 min−1) with NO-inhalation (50 p.p.m.) completely prevented the fall in MABP, significantly improved CO, and attenuated the biphasic increase in MPAP and PVR. 4 Endotoxin also caused a decline in Pao2 and a rise of Paco2. Infusion of l-NMMA neither affected the fall in Pao2 nor the increase in Paco2. In contrast, inhalation with NO gas alone as well as the combined administration of l-NMMA infusion and NO-inhalation completely prevented the fall in Pao2 and significantly protected against the increase in Paco2. 5 Infusion of endotoxin for 180 min resulted in a mortality of 58%, which was not affected by l-NMMA (63%). In contrast, treatment of LPS-animals with either NO-inhalation alone or NO-inhalation plus l-NMMA completely prevented mortality. 6 This investigation demonstrates that treatment with NO-inhalation, in order to prevent the dramatic increase in MPAP, PVR and the alterations in peripheral blood gases combined with systemic l-NMMA to improve systemic MABP and thus organ perfusion, may be a new therapeutic regimen in the treatment of septic shock.

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock.

1. The present investigation compares the effects of intravenous infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) with that of an inhalation with NO gas in a porcine model of endotoxin (lipopolysaccharide, LPS) shock. In addition, the effects of the combination of these two treatments were also investigated. 2. Male pigs were anaesthetized and instrumented for the measurement of haemodynamic parameters. Blood samples were withdrawn at different time intervals for determination of blood gases, pH, and plasma levels of nitrite/nitrate and tumour necrosis factor. 3. Endotoxin infusion (15 micrograms kg-1 h-1 for 3 h) caused a progressive fall in mean arterial blood pressure (MABP) and cardiac output (CO) and a biphasic increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). A continuous infusion of L-NMMA (0.1 mg kg-1 min-1) significantly attenuated the fall in MABP, but did not affect MPAP, CO and PVR. NO-inhalation (50 p.p.m.) did not affect MABP, but significantly blunted the biphasic increase in MPAP and PVR and significantly delayed the fall in CO. The combination of L-NMMA infusion (0.1 mg kg-1 min-1) with NO-inhalation (50 p.p.m.) completely prevented the fall in MABP, significantly improved CO, and attenuated the biphasic increase in MPAP and PVR. 4. Endotoxin also caused a decline in PaO2 and a rise of PaCO2. Infusion of L-NMMA neither affected the fall in PaO2 nor the increase in PaCO2. In contrast, inhalation with NO gas alone as well as the combined administration of L-NMMA infusion and NO-inhalation completely prevented the fall in Pao2 and significantly protected against the increase in Paco2.5. Infusion of endotoxin for 180 min resulted in a mortality of 58%, which was not affected by L-NMMA (63%). In contrast, treatment of LPS-animals with either NO-inhalation alone or NO inhalation plus L-NMMA completely prevented mortality.6. This investigation demonstrates that treatment with NO-inhalation, in order to prevent the dramatic increase in MPAP, PVR and the alterations in peripheral blood gases combined with systemic L-NMMAto improve systemic MABP and thus organ perfusion, may be a new therapeutic regimen in the treatment of septic shock.

Effect of Early versus Delayed Hypoxic Environment on Neonatal Rabbits

We developed a low-cost, nonsurgical small animal model simulating the condition of cyanotic heart disease. Six groups of New Zealand white rabbits were studied: Group (1-C), 1-week-old control rabbits (n = 9) reared in room air; Group (1-H), 1-week-old rabbits placed in a hypoxic environment (10% O2) at birth (n = 5); Group (1-H-3), 1-week-old rabbits (n = 11) reared in room air for 3 days and then placed under hypoxic conditions identical to those for Group (1-C); Group (4-C), 4-week-old control rabbits (n = 12); Group (4-H), 4-week-old rabbits placed in hypoxia since birth (n = 11); Group (4-H-3), 4-week-old rabbits kept in room air after birth for 3 days (n = 7) before being exposed to hypoxia. Animals were anesthetized, heparinized, and instrumented for measurement of hemodynamic parameters. Right ventricular (RV) hypertrophy and hematocrit were assessed. Lung tissue was analyzed using quantitative morphometric techniques to assess arterial size, number, and muscularity. Group (1-H) and Group (4-H) developed RV hypertrophy, pulmonary hypertension, and erythrocytosis. The RV hypertrophy developed rapidly, as early as 1 week of age and became so pronounced by 4 weeks as to result in high mortality rate (35%). None of the animals in Groups (1-H-3) or (4-H-3) died while chronic changes of hypoxemia still developed. Placing rabbits after birth in room air for 3 days before exposing them to hypoxia appeared to play a protective role, moderating the development of pulmonary hypertension and severe RV hypertrophy. The effects of hypoxia appear to be at least partially dependent on the time of exposure. Utilizing our low-cost model will allow future work, including study of the effects of chronic hypoxemia on systemic ventricle exposed to an ischemic insult.

Quality Assurance in Hemodynamic Monitoring

Patient care management decisions frequently are based, at least in part, on hemodynamic indices. Accuracy in repeated measurement of hemodynamic parameters is therefore critical. It can be achieved only through a program of quality assurance (QA), which should include the following factors: static, dynamic, and validation of pulmonary artery wedge pressure (PAWP). The static QA factor consists of establishing an accurate reference point from which all subsequent measurements are made. The hemodynamic monitoring system must be able to transmit pulsating physiologic pressures to the transducer with high fidelity, which is validated via the dynamic response or "square wave" test and damping coefficient. Other QA aspects that are used to validate the accuracy of PAWP include catheter placement into lung zone 3 capillary and comparison of capillary to arterial blood gases. Measurement error also can be introduced because of varying methods to quantify the ana-log pressure waveforms, such as end-expiratory or pressure averaging techniques. This paper explores each of these domains within a framework of quality assurance.

Effects of halothane and isoflurane on beta‐endorphin release in children

We compared the effects of halothane and isoflurane with 50% nitrous oxide (seven children each) on plasma beta-endorphin concentrations in a group of 14 children aged 1 to 6 years. The findings were compared for four periods of anaesthesia: basal, induction, maintenance and recovery. Beta-endorphin release was most increased with isoflurane, especially during the maintenance period. Measurements of haemodynamic parameters (heart rate and blood pressure) showed diastolic blood pressure significantly lower after isoflurane anaesthesia. The findings suggest that the use of isoflurane for paediatric inhaled isoflurane anaesthesia leads to a more marked surgical stress adaptation effect than the use of halothane.