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Interpretation of oxygen disappearance curves measured in blood perfused tissues.

We have developed a two compartment (tissue and blood) lumped parameter model to interpret oxygen disappearance curves (O2 DCs) measured in vivo with PO2 microelectrodes in tissues which are perfused with blood. To include the properties of the oxyhemoglobin equilibrium curve (HEC), we used an algorithm we have recently developed for both standard and nonstandard conditions. The new blood and tissue model is more useful than a previous analysis using the Hill equation for blood and constant oxygen consumption (VO2). The model can be adapted for constant (zero-order) consumption, Michelis-Menten kinetics, or for double cytochrome systems. Examples for the former include brain, and for the latter, carotid body. The models are discussed in relationship to experimental microelectrode measurements in gerbil brain and in cat carotid body after blood flow occlusion.

Animals↗

Stress thallium myocardial scintigraphy. Accurate marker of myocardial tissue perfusion.

Assessment of myocardial blood flow has been the subject of extensive research and study, ever since coronary artery disease has been recognised as a first rate killer of mankind. Non-invasive methods like routine ECG, exercise ECG, 2-D echocardiography lack sensitivity and specificity. The specificity of exercise ECG becomes less in patients with ventricular hypertrophy, intraventricular conduction delay, left bundle branch block (LBBB), previous myocardial infarction, subendocardial infarction, non specific ST-T changes at rest and exercise, and electrolyte imbalance; those taking various drugs such as digitalis and quinidine; and in evaluation of post bypass graft or post PTCA (percutaneous transluminal coronary angioplasty) status. Coronary angiography, which is an invasive procedure, provides direct proof of the presence and extent of coronary artery disease in the form of anatomical changes like luminal narrowing. It fails to give any information regarding small vessel disease or bridging of vessels in the cardiac musculature and in those with normal coronaries with anginal pain at stress. It also fails to provide direct information regarding myocardial tissue perfusion, which ultimately decides the outcome of the disease. In addition, coronary angiography involves some percentage of risk to the patient. It is in this context that thallium 201 myocardial scintigraphy occupies a unique position. It has none of the disadvantages of exercise ECG and it directly reflects myocardial perfusion at the tissue level. Stress thallium 201 scintigraphy directly quantitates the amount of myocardium involved as a result of previous myocardial infarction or ischaemia, unlike stress ECG and other non-invasive modalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation↗

Steady-state analysis and evaluation of a new thermal sensor for surface measurements of tissue perfusion.

The steady-state response and operating characteristics of a new thermal sensor for surface measurements of local tissue perfusion have been analyzed theoretically and evaluated in vivo. The flow measurement system incorporates an electrically isolated thin-film thermal sensor, which is maintained at a fixed temperature by high frequency response electronic circuitry. The sensor rests on the tissue surface, and the power required to maintain a fixed probe to tissue temperature elevation is measured and related to tissue blood flow. A theoretical analysis of the steady-state probe response to flow changes was carried out employing the bio-heat-transfer equation and a solution based on Fourier series to describe the temperature distribution within the tissue domain. A comparison of steady-state theory to results obtained from initial experimental tests on the surface of the dog heart, over a perfusion range 0.51 to 2,00 ml/min/g, shows close agreement. The probe demonstrates good sensitivity to flow changes, provides stable and continuous measurements, and appears promising for both research and clinical applications.

Animals↗

Comparison of transcranial brain tissue perfusion images between ultraharmonic, second harmonic, and power harmonic imaging.

BACKGROUND AND PURPOSE: To clarify optimal brain tissue perfusion images visualized by transcranial ultrasound harmonic imaging, we compared gray-scale integrated backscatter (IBS) images of new ultraharmonic imaging (UHI) and conventional second harmonic imaging (SHI) with power harmonic imaging (PHI) (harmonic B-mode with harmonic power Doppler images) in 10 patients with and 4 without a temporal skull. METHODS: Using a SONOS 5500 (Philips), we evaluated transient response images taken after a bolus Levovist injection at a horizontal diencephalic plane via temporal windows. Based on transmitting/receiving frequencies (MHz), 4 imaging procedures using an S3 transducer (SHI2.6 [1.3/2.6], UHI [1.3/3.6], PHI2.6 [1.3/2.6], and PHI3.2 [1.6/3.2]) and 2 imaging procedures using an S4 transducer (SHI3.6 [1.8/3.6] and PHI3.6 [1.8/3.6]) were compared in terms of size and location, peak intensity (PI), contrast area demarcation, and background image quality. RESULTS: In intact skull cases, gray-scale imaging tended to show larger contrast areas than PHI. A large contrast area was most frequently observed in SHI2.6 images, despite there being more high-PI cases in UHI. No contrast area with unclear background was observed in a few cases. In craniectomized cases, all contrast images tended to have large and high PI compared with the intact skull cases. PHI, particularly PHI3.6, demonstrated sharper demarcation and a clearer background than gray-scale imaging. CONCLUSIONS: Transcranial gray-scale SHI using a low receiving frequency of 2.6 MHz is the superior method. PHI identifies contrast area localization better than gray-scale imaging and is particularly suitable for intraoperative and postoperative cases.

Adult↗

Relationship between arterial diameter and perfused tissue volume in myocardial microcirculation: a micro-CT-based analysis.

The volume of myocardial tissue that is perfused by an epicardial coronary artery has been shown to be predictably related to the diameter of the epicardial arterial lumen. However, to what extent the intramyocardial microvasculature follows the epicardial rules remains unclear. To explore the relationship between the diameter of coronary arterioles and their subsequent perfused myocardial volumes, we quantified the volume of nonperfused myocardium resulting from an embolized arteriole of a certain diameter. We injected a single dose of microspheres selected from one of nine possible microsphere combinations (10, 30, and 100 microm diameter, each at three possible doses) into the left anterior descending coronary and/or left circumflex arteries of seven anesthetized pigs. At postmortem, the coronary arteries were infused with a radiopaque silicon polymer. Embolized myocardium (1 cm(3)) was scanned with a microcomputerized tomography scanner and resulted in three-dimensional images that consisted of 20 microm/side cubic voxels and a subvolume of the specimen with 4 microm/side cubic voxels. Image analysis provided the number and volumes of myocardial perfusion defects for each size and dose of microspheres. The smallest individual myocardial perfusion defects, which correspond to the volume of myocardium perfused by a single embolized arteriole, were found to be 0.0004 +/- 0.0002, 0.02 +/- 0.004, and 0.62 +/- 0.099 mm(3) for the 10-, 30-, and 100-microm microspheres, respectively. The number of myocardial perfusion defects in the embolized myocardium was inversely related to the dose of the injected microspheres. This reflects a clustering behavior that is consistent with a random distribution process of the individual embolized perfusion defects.

Animals↗

Impact of scar on water-perfusable tissue index in chronic ischemic heart disease: Evaluation with PET and contrast-enhanced MRI.

BACKGROUND: The water-perfusable tissue index (PTI) is assumed to differentiate viable myocardium from scar tissue, but histological comparisons in humans are lacking. The present study compares PTI with delayed contrast-enhanced magnetic resonance imaging (DCE-MRI), a validated marker of fibrotic tissue, in patients with ischemic left ventricular (LV) dysfunction. In addition, the optimal PTI threshold for detection of myocardial viability was defined when DCE-MRI was taken as a reference. MATERIALS: Twenty patients with ischemic LV dysfunction were studied with positron emission tomography, using oxygen-15-labeled water and carbon monoxide as tracers, and DCE-MRI. RESULTS: Of the 200 analyzed segments, 112 demonstrated DCE and were subsequently divided in three subgroups according to the severity of enhancement. PTI was 1.04 +/- 0.21 in control segments and gradually decreased with increasing extent of DCE to 0.77 +/- 0.31 for segments with transmural enhancement (p < 0.001). However, PTI progressively underestimated infarct size with increasing quantities of scar tissue (r = 0.61, p < 0.01). A PTI cutoff value of 0.89 yielded the best diagnostic accuracy for detection of myocardial viability with sensitivity and specificity values of 75 and 77%, respectively. CONCLUSIONS: PTI is inversely related to the extent of scar tissue estimated by DCE-MRI in patients with chronic ischemic heart disease and LV dysfunction. However, with increasing quantities of scar tissue, PTI overestimates the extent of residual viable tissue. A PTI threshold of 0.89 yields the best diagnostic accuracy for viability detection.

Aged↗

Sublingual capnometry and indexes of tissue perfusion in patients with circulatory failure.

OBJECTIVE: To examine the relationship between sublingual PCO(2) (PslCO(2)) and other indexes of tissue perfusion. DESIGN: Prospective observational study. SETTING: Medical and coronary ICUs in a tertiary-care teaching hospital. SUBJECTS: Twenty-five patients with circulatory failure, 19 patients with sepsis, and 6 patients with cardiac failure. MEASUREMENTS AND MAIN RESULTS: PslCO(2), gastric intramucosal PCO(2) (PiCO(2)), arterial lactate concentration, systemic oxygen delivery, and systemic oxygen consumption were measured at baseline and at 1, 3, 6, 12, and 24 h after the beginning of the study. PslCO(2) and the PslCO(2)-PaCO(2) gradient were increased but not significantly different in nonsurvivors compared to survivors at baseline. At 24 h, the mean (+/- SE) PslCO(2) was 45 +/- 4 mm Hg in survivors and 61 +/- 4 mm Hg in nonsurvivors (p = 0.06), while the PslCO(2)-PaCO(2) gradient was 14 +/- 3 mm Hg in survivors and 29 +/- 4 mm Hg in nonsurvivors (p < 0.05). No other significant differences in survivors and nonsurvivors were observed in any other index of perfusion. For all patients, the correlations between PslCO(2) and PiCO(2) (r = 0.459; p < 0.05) and cardiac index (r = 0.285; p < 0.05) were observed. The PslCO(2)-PaCO(2) gradient also was correlated with the PiCO(2)-PaCO(2) gradient (r = 0.323; p < 0.05). When patients were placed into subsets of sepsis and cardiac failure, the strength of the correlations increased in the patients with cardiac failure (PslCO(2) vs lactate, r = 0.611 and p < 0.05; PslCO(2) vs PiCO(2), r = 0.613 and p < 0.05; PslCO(2) vs PiCO(2)-PaCO(2) gradient, r = 0.648 and p < 0.05). CONCLUSION: PslCO(2) correlated best with PiCO(2) and arterial lactate concentration in patients with cardiac failure. PslCO(2) and the PslCO(2)-PaCO(2) gradient may be useful as indexes of the severity of perfusion failure.

APACHE↗

Effects of the radiosensitising agent nicotinamide on relative tissue perfusion and kidney function in C3H mice.

Nicotinamide is an effective radiosensitiser of murine tumours, functioning by improving tumour perfusion by decreasing the proportion of intermittently closed capillaries. The effect of nicotinamide on relative tissue perfusion of RIF-1 tumour and normal skin, muscle, lung, liver, kidney and spleen were investigated using the 86Rb extraction technique. A dose of 1000 mg/kg was shown to have transient effects on tumour, skin and lung perfusion but to have sustained effects on muscle (a drop to 80% of control), liver, kidney and spleen (with increases ranging from 165% to 280% of control) from 0.5 to 4 h after treatment i.e. during the period of maximum radiosensitisation. These increases were evident at doses as low as 100 mg/kg. The data suggest that the radiosensitisation induced by nicotinamide in the mouse may be associated with these perfusion changes. Nicotinamide was also shown to have a substantial inhibitory effect on renal function, inhibiting 51CrEDTA clearance by a factor (+/- 2 SE) of 2.56 +/- 0.19 and 125I-iodohippurate clearance by a factor of 2.07 +/- 0.45 at 1000 mg/kg. These effects were shown to be dose-related, and to be evident at doses from 400 mg/kg upwards. This suggests that nicotinamide potentiation of co-administered cytotoxic agents may be mediated by reduced renal clearance of the cytotoxic drug, thus increasing the plasma half-life.

Animals↗

BW12C: effects on tumour hypoxia, tumour thermosensitivity and relative tumour and normal tissue perfusion in C3H mice.

BW12C (5-[2-formyl-3-hydroxypenoxyl] pentanoic acid) is an agent which stabilises oxyhaemoglobin and thus reduces oxygen delivery to tissues. It is of interest as a possible potentiator of bioreductive agents and/or hyperthermia. The increases in radiobiological hypoxic fraction of RIF-1 and KHT tumours 30 min after 70 mg kg-1 BW12C i.v. were measured and shown to be similar; factors (+/- 2 s.e.) ranged from 3.87 (2.84-5.29) to 5.92 (1.92-18.2) despite the large variation in initial hypoxic fraction, from 0.30 (0.18-0.50) % for RIF-1 intramuscularly in the leg to 16.3 (14.7-18.1) % for subcutaneous KHT flank tumours. Thermosensitivity of intramuscular KHT leg tumours was not enhanced by 70 mg kg-1 BW12C 30 min before heating at 43 degrees C, 43.5 degrees C or 44 degrees C, assayed by regrowth delay. The effect of 70 mg kg-1 BW12C on relative tissue perfusion (RTP), assayed by 86Rb extraction, was measured from 0.5 h to 6 h after treatment. After 1 h RTP (+/- 2 s.e.) in RIF-1 tumours was reduced to 84 +/- 5.7% and 68 +/- 9.6% of control in leg and flank tumours respectively, and to 86 +/- 6.4% in leg muscle while flank skin RTP was unaltered at 109 +/- 8.6%. There were substantial increases in kidney (149 +/- 10.7%) spleen (173 +/- 22.1%) and lung (128 +/- 10.4%) at 1 h but in liver there was a decrease at 2 h to 85 +/- 8.4%. Dose response studies showed that the threshold dose for reduction of tumour RTP is between 55 and 70 mg kg-1, but perturbations in normal tissue RTP occur at lower doses, e.g. 40 mg kg-1 for spleen. BW12C had minimal effects on renal function measured by 51CrEDTA clearance. The data as a whole indicate that reduction in tumour perfusion is likely to be an important determinant in the increase in tumour hypoxia induced by BW12C.

Animals↗

Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke: relation to clinical outcome.

BACKGROUND: One major therapeutic strategy to minimise the extent of infarction after ischaemic stroke is to improve early reperfusion using thrombolytic agents. However, reperfusion may be hazardous and the period during which reperfusion may have a beneficial effect on tissue and clinical outcome is not known. METHODS: Fifty three patients were studied with serial cerebral perfusion (99mTcHMPAO SPECT) during the first 48 hours of ischaemic stroke to determine if changes in tissue perfusion during this time were prognostically significant. Single and multiple linear regression non-parametric analyses were used to include other factors during the same period which may influence outcome. RESULTS: In univariate analysis age, neurological score at admission, SPECT perfusion defect size in the first 24 hours, and percentage change in cerebral tissue perfusion at 24-48 hours (all P < 0.01) correlated significantly with the Barthel score at three months. In multiple linear regression analysis only age (P < 0.01) and percentage change in cerebral tissue perfusion at 24-48 hours (P < 0.01) provided independent prognostic information at three months. CONCLUSIONS: Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke are significant outcome predictors and therapeutic effort aimed at increasing perfusion during this period seem to be justified.

Aged↗

[Do strong static magnetic fields in NMR tomography modify tissue perfusion?].

Findings obtained in humans and test animals raised the question whether strong static magnetic fields as used in NMR-tomography may affect tissue perfusion. In two test series including 20 subjects, each skin blood flow at the thumb was determined by heat clearance, and forearm blood flow was measured by venous occlusion plethysmography. For comparative purposes, measurements were carried out bilaterally at both extremities. The experiments consisted of three sections that lasted 10 min each. During the second section the thumb or the forearm were unilaterally exposed to magnetic fields of 0.9 to 1 T and 0.4 to 0.5 T, respectively. The results of this section were compared with the values obtained during the experimental sections prior to and after the exposure to the magnetic field. The results were also compared with the blood flow measured at the contralateral extremity. Neither at the skin of the thumb nor at the forearm were there changes in local blood flow attributable to the magnetic fields applied.

Adult↗

Arterial pH and carbon dioxide tension as indicators of tissue perfusion during cardiac arrest in a canine model.

BACKGROUND AND METHODS: Previous studies have shown that Paco2 and end-tidal CO2 reflect coronary artery perfusion pressures during cardiac arrest. We investigated the relationship of coronary artery perfusion pressure to central arterial pH and Paco2 values during resuscitation from cardiac arrest in a canine model. Twenty-four mongrel dogs were block randomized to three different resuscitation groups after induction of ventricular fibrillation and cardiac arrest: a) standard cardiopulmonary resuscitation (CPR) and advanced life support (n = 8); b) cardiopulmonary bypass (n = 8); or c) open-chest CPR (n = 8). Central arterial blood gases and perfusion pressures were monitored during cardiac arrest and during resuscitation. RESULTS: Prearrest blood gases and hemodynamic values were similar between groups. Sixteen dogs from all three groups were successfully resuscitated. Survivors had significantly higher coronary artery perfusion pressure (p = .03), Paco2 (p = .015), and lower pH (p = .01) values than nonsurvivors. There was no correlation of pH and Paco2 during mechanical external CPR. However, after institution of the different resuscitation techniques, pH and Paco2 each showed a statistically significant correlation (r2 = .50 and .33, respectively) with coronary artery perfusion pressure. CONCLUSIONS: Central arterial pH and Paco2 monitoring during cardiac arrest may reflect the adequacy of tissue perfusion during resuscitation and may predict resuscitation outcome from ventricular fibrillation.

Animals↗

Regional blood flow during acute heart failure in dogs. Role of adipose tissue perfusion in regulating plasma-free fatty acids.

The effect of acute ischaemic left ventricular failure on regional blood flow and the possible role of adipose tissue perfusion in the regulation of plasma FFA during failure were examined. Left ventricular failure was induced in closed-chest anaesthetized dogs by injection of 50 micrometer plastic microspheres into the left main coronary artery. Regional blood flow, measured with tracer microspheres, showed a redistribution of cardiac output after the induction of failure. Adipose cardiac output (P less than 0.05), while skeletal muscle and pancreatic blood flow decreased about in proportion to the decrease in cardiac output. There was only a moderate decrease in renal blood flow and in left ventricular myocardial blood flow. In the free wall of the right ventricle blood flow was unchanged. There was a marked decrease in plasma FFA during failure (P less than 0.05), which could not be attributed to enhanced FFA turnover rate nor to inhibition of adipose tissue lipolysis, as plasma glycerol tended to increase. The marked decrease in adipose tissue blood flow during failure suggests that plasma FFA decreased due to trapping of FFA in adipose tissue.

Adipose Tissue↗

Impact of systemic depulsation on tissue perfusion and sympathetic nerve activity.

BACKGROUND: We postulated that pathophysiologic processes under nonpulsatile circulation are related to the behavior of the sympathetic nerve activity that regulates tissue perfusion. METHODS: Pulsatile and nonpulsatile pumps were installed in parallel in the left heart bypass circuit of anesthetized goats (n = 9) so that pulsatile circulation could be converted to nonpulsatile circulation instantly. At 5 minutes before and after systemic depulsation, we measured hemodynamic indices, renal nerve activity, and regional blood flow of the brain, heart, and renal cortex. RESULTS: Renal nerve activity was significantly elevated after systemic depulsation (15.6 +/- 9.3 versus 19.4 +/- 9.8 microV), when mean aortic pressure remained almost constant. The renal cortical flow was significantly reduced after depulsation (3.61 +/- 1.23 versus 2.93 +/- 1.19 mL.min-1.g-1), whereas no significant difference was found in the regional blood flow of the brain or the heart. CONCLUSIONS: The significant reduction of renal cortical blood flow after systemic depulsation is associated with a significant increase in renal nerve activity. Our results suggest that increased renal nerve activity plays an important role in the reduction of renal function after systemic depulsation.

Animals↗

[Quantification of tissue perfusion with novel ultrasound methods].

Perfusion describes an important parameter of tissue vitality, e. g. of the myocardium, brain, or the kidney. In malign tumours, perfusion is of particular interest for characterization and prognosis. In addition, new pro- or anti-angiogenic therapies require a functional imaging which is suitable to quantify vascularity. Sonographic methods for the detection of microvascularity, particularly related smaller than those amenable to Doppler ultrasound, are reviewed. The main focus deals with the explanation of contrast-enhanced sonography using replenishment kinetics of microbubbles which provides a comprehensive quantification of tissue perfusion. Alterations of the microvascularity e. g., under anti-angiogenic therapy, can be depicted in experimental studies using this novel approach. Further clinical applications can be the quantification of the perfusion in the myocardium, the brain, or the kidney. New approaches to optimize the theoretical model to describe the replenishment, and novel technical developments are discussed.

Animals↗

Interaction between beta-adrenergic receptor stimulation and nitric oxide release on tissue perfusion and metabolism.

Nitric oxide (NO) may be an important modulator of sympathetic tone. We used im and sc microdialysis in humans to characterize the interaction of NO synthase inhibition and adrenoreceptor stimulation on tissue perfusion, metabolism, and norepinephrine release. Microdialysis probes were perfused with L- or D-nitro-L-arginine-methyl-ester (100 micromol/L) followed by incremental doses of isoproterenol, epinephrine, or nitroprusside. Blood flow was estimated based on the ethanol dilution technique. In muscle, the increase in blood flow with isoproterenol was abolished by L-NAME. The ethanol ratio was 0.03 +/- 0.011 with D-NAME and 0.075 +/- 0.014 with L-NAME during isoproterenol treatment (1 micromol/L). The effect was less pronounced in adipose tissue. The vasodilatory effect of nitroprusside was similar with D- and L-NAME. L-NAME augmented isoproterenol- and epinephrine-induced glycerol release. Dialysate glycerol during 1 micromol/L isoproterenol was 47 +/- 6.7 micromol/L with D-NAME and 72 +/- 15 micromol/L with L-NAME. In skeletal muscle, dialysate norepinephrine during 1 micromol/L isoproterenol treatment was 0.73 +/- 0.17 and 1.3 +/- 0.15 nmol/L with D- and L-NAME, respectively. We conclude that NO synthase inhibition attenuates beta(2)-adrenoreceptor-mediated vasodilation and enhances beta-adrenoreceptor-mediated lipolysis. These effects are in part mediated through an increase in interstitial norepinephrine concentrations. The data are consistent with the idea that in humans, NO is important in modulating and ameliorating sympathetic effects in peripheral tissues.

Adrenergic beta-Agonists↗

A quantitative analysis of alternated line scanning in k space and its application in MRI of regional tissue perfusion by arterial spin labeling.

A quantitative analysis of the alternated-line-scanning method is performed for k-space data acquisition in MRI. Application of the method in MRI of regional tissue perfusion by arterial spin labeling is demonstrated. It is also shown that, by using the alternated-line-scanning method, the degree of arterial spin labeling alpha can be determined in a single scan.

Animals↗

Optimisation of oxygenation and tissue perfusion in surgical patients.

Surgical patients with limited cardiovascular reserve have much worse prognosis than patients with normal hearts. This review identifies 17 randomised controlled clinical trials that have investigated peri-operative therapy designed to increase tissue perfusion in surgical patients, many of whom have limited cardiovascular reserve. Although there are differences which make equating the trials complex, a total of 1974 patients have been enrolled in the studies and the odds ratio for reduction in mortality is 0.45 (95% confidence intervals 0.33-0.60). Further research needs to be undertaken in the identification of patients with limited cardiovascular reserve and for investigating proposed treatment strategies. Despite this, it appears that such patients have improved outcome if they are admitted to intensive care unit pre-operatively and have suitable therapy given to improve tissue oxygen delivery.

Blood Circulation↗