The microcirculation of myocutaneous island flaps in pigs studied with radioactive blood volume tracers and microspheres of different sizes.

In order to further improve the understanding of hemodynamic changes in the immediate postoperative phase after elevation of myocutaneous flaps, regional blood flow and arteriovenous (A-V) shunting were measured in rectus abdominis island flaps in 8 pigs. Radioactive microspheres of two sizes (15 and 50 micron) were used. Approximately half (53.4 +/- 6 percent) of the 15-micron microspheres and one-fourth (24.1 +/- 6 percent) of the 50-micron microspheres entering the flap appeared in the venous outflow. Compared with the control area, A-V shunting was significantly increased in muscle and substantially more pronounced in skin. Nutritional blood flow, total blood flow, and vascular volume were increased in muscle and unchanged in skin and subcutis. The lowest tissue hematocrit of 7 +/- 1 percent was found in skin as compared with a central hematocrit of 35 +/- 2 percent. Tissue hematocrit in flap muscle was decreased to 17 +/- 2 percent when compared with control muscle (22 +/- 3 percent), and the mean transit time for blood was correspondingly decreased. Thus vasodilation provided increased perfusion through muscular capillaries and through A-V shunts. Shunting of 15-micron microspheres appeared to take place not only in skin, but also in subcutis and muscle, which challenges the widespread belief that A-V shunting does not occur in muscle.     

Chronic CO inhalation and carotid body catecholamines: testing of hypotheses

The purpose of this study was twofold: one concerns carotid blood flow and tissue PO2 and the other the effect of chronic hypoxic hypoxia on enhanced catecholamine content. The rationale was that chronic CO inhalation would not mimic the effect of hypoxia on the carotid body if its tissue blood flow is sufficiently high to counteract the effect of CO on O2 delivery and, hence, on tissue PO2. The differential effects of CO on the carotid body and erythropoietin-producing tissue would also indicate that the effect of hypoxic hypoxia on the carotid body is the result of a direct action of a local low O2 stimulus rather than secondary to a systemic effect initiated by other O2-sensing tissues. To test these alternatives we studied the effects of chronic CO inhalation on carotid body catecholamine content and hematocrit in the rats, which were exposed to an inspired PCO of 0.4-0.5 Torr at an inspired PO2 of approximately 150 Torr for 22 days. The hematocrit of CO-exposed rats was 75 +/- 1.1% compared with 48 +/- 0.7% in controls. Dopamine and norepinephrine content of the carotid bodies (per pair) was 5.88 +/- 0.91 and 3.02 +/- 0.19 ng, respectively, in the CO-exposed rats compared with 6.20 +/- 1.0 and 3.29 +/- 0.6 ng, respectively, in the controls. Protein content of the carotid bodies (per pair) was 18.4 +/- 1.6 and 20.5 +/- 0.9 micrograms, respectively. Thus, despite a vigorous erythropoietic response, the CO-exposed rats failed to show any significant stimulation of carotid body in terms of the content of either catecholamine or protein. The results suggest that carotid body tissue PO2 is not compromised by moderate carboxyhemoglobinemia because of its high tissue blood flow and that the chronic effect of hypoxic hypoxia on carotid body is direct.     

Effect of cold and warm dry air hyperventilation on canine airway blood flow

Tracheobronchial blood flow increases with cold air hyperventilation in the dog. The present study was designed to determine whether the cooling or the drying of the airway mucosa was the principal stimulus for this response. Six anesthetized dogs (group 1) were subjected to four periods of eucapnic hyperventilation for 30 min with warm humid air [100% relative humidity (rh)], cold dry air (-12 degrees C, 0% rh), warm humid air, and warm dry air (43 degrees C, 0% rh). Five minutes before the end of each period of hyperventilation, tracheal and central airway blood flow was determined using four differently labeled 15-micron diam radioactive microspheres. We studied another three dogs (group 2) in which 15- and 50-micron microspheres were injected simultaneously to determine whether there were any arteriovenous communications in the bronchovasculature greater than 15 micron diam. After the last measurements had been made, all dogs were killed, and the lungs, including the trachea, were excised and blood flow to the trachea, left lung bronchi, and parenchyma was calculated. Warm dry air hyperventilation produced a consistently greater increase in tracheobronchial blood flow (P less than 0.01) than cold dry air hyperventilation, despite the fact that there was a smaller fall (6 degrees C) in tracheal tissue temperature during warm dry air hyperventilation than during cold dry air hyperventilation (11 degrees C), suggesting that drying may be a more important stimulus than cold for increasing airway blood flow. In group 2, the 15-micron microspheres accurately reflected the distribution of airway blood flow but did not always give reliable measurements of parenchymal blood flow.     

Tracheobronchial perfusion during exercise in ponies

Tracheobronchial circulation during exercise has previously not been examined. Therefore blood flow to the trachea and bronchi (up to 7th generation of branching) was studied in seven healthy adult ponies at rest and during the 3rd and 10th min of exercise performed at a treadmill speed setting of 25 km/h. The ambient air temperature varied from 19 to 20 degrees C and humidity from 35 to 45%. To determine blood flow radionuclide-labeled 15-microns-diameter microspheres were injected into the left ventricle via a catheter advanced from the left carotid artery (exposed using local anesthesia), and a reference sample was obtained from the aorta. Adequate mixing of microspheres with blood was demonstrated by similar perfusion values for left and right kidneys. Exercise increased heart rate (194 +/- 9 and 200 +/- 7 beats/min) and mean aortic pressure (169 +/- 8 and 156 +/- 4 mmHg) of ponies at 3rd and 10th min. Tracheal blood flow (6.7 +/- 0.5 ml.min-1 x 100 g-1) of resting ponies was only one-third of the bronchial blood flow (21.6 +/- 4.9 ml.min-1 x 100 g-1) Significant changes in tracheal perfusion did not occur at 3rd or 10th min of exercise. Although bronchial perfusion also did not change at the 3rd min of exercise, it rose dramatically to 202.8 +/- 30.3 ml.min-1 x 100 g-1 during the 10th min. Concomitantly, renal blood flow decreased at 10th min of exertion. The large increase in bronchial blood flow at 10th min of exertion may have been necessitated by the need to help dissipate body heat.     

Effects of coronary sinus pressure elevation on coronary blood flow distribution in dogs with normal preload

Coronary sinus pressure (Pcs) elevation shifts the diastolic coronary pressure-flow relation (PFR) of the entire left ventricular myocardium to a higher pressure intercept. This finding suggests that Pcs is one determinant of zero-flow pressure (Pzf) and challenges the existence of a vascular waterfall mechanism in the coronary circulation. To determine whether coronary sinus or tissue pressure is the effective coronary back pressure in different layers of the left ventricular myocardium, the effect of increasing Pcs was studied while left ventricular preload was low. PFRs were determined experimentally by graded constriction of the circumflex coronary artery while measuring flow using a flowmeter. Transmural myocardial blood flow distribution was studied (15-micron radioactive spheres) at steady state, during maximal coronary artery vasodilatation at three points on the linear portion of the circumflex PFR both at low and high diastolic Pcs (7 +/- 3 vs. 22 +/- 5 mmHg; p less than 0.0001) (1 mmHg = 133.322 Pa). In the uninstrumented anterior wall the blood flow measurements were obtained in triplicate at the two Pcs levels. From low to high Pcs, mean aortic (98 +/- 23 mmHg) and left atrial (5 +/- 3 mmHg) pressure, percent diastolic time (49 +/- 7%), percent left ventricular wall thickening (32 +/- 4%), and percent myocardial lactate extraction (15 +/- 12%) were not significantly changed. Increasing Pcs did not alter the slope of the PFR; however, the Pzf increased in the subepicardial layer (p less than 0.0001), whereas in the subendocardial layer Pzf did not change significantly. Similar slopes and Pzf were observed for the PFR of both total myocardial mass and subepicardial region at low and high Pcs. Subendocardial:subepicardial blood flow ratios increased for each set of measurements when Pcs was elevated (p less than 0.0001), owing to a reduction of subepicardial blood flow; however, subendocardial blood flow remained unchanged, while starting in the subepicardium toward midmyocardium blood flow decreased at high Pcs. This pattern was similar for the uninstrumented anterior wall as well as in the posterior wall. Thus as Pcs increases it becomes the effective coronary back pressure with decreasing magnitude from the subepicardium toward the subendocardium of the left ventricle. Assuming that elevating Pcs results in transmural elevation in coronary venous pressure, these findings support the hypothesis of a differential intramyocardial waterfall mechanism with greater subendo- than subepi-cardial tissue pressure.     

Measurement of bronchial blood flow with radioactive microspheres in awake sheep

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood flow measurements by the reference sample method with microsphere injection in to the aorta: an accurate and easy approach.

The validity of hemodynamic measurements by the reference sample method with microspheres injection into the aorta, via a carotid artery catheter, was evaluated in rats and compared with the results obtained after left ventricle injection. In the aorta injection group, a good mix of microspheres was observed in 83% of the animals. Moreover, a symmetrical distribution of microspheres was observed in 10 out of 12 rats (83%). An excellent correlation between right and left kidney-testes blood flows was observed (r = 0.93 and 0.96, respectively; P less than 0.01). Mean arterial pressure was not modified during microspheres injection into the aorta. Cardiac output (104 +/- 26 vs 101 +/- 23 ml/min, NS) and portal blood flow (14.2 +/- 3.3 vs 13.5 +/- 2.2 ml/min, NS) were similar after aorta and left ventricle injections series, respectively. Our results indicate that the injection of microspheres into the aorta is an adequate and easy approach to systemic and splanchnic hemodynamic measurements. This approach could be a good alternative to left ventricle injection of microspheres in experimental studies in rats.     

Chronic CO exposure stimulates erythropoiesis but not glomus cell growth

The effect of chronic CO exposure, which stimulates erythropoietin production and erythropoiesis, was studied on carotid body cells in the rat. The hypothesis to be tested was that chronic CO inhalation would stimulate cellular hypertrophy and hyperplasia of carotid body if it caused local tissue hypoxia as in chronic hypoxia. The failure of an appropriate response would indicate a lack of a specific local effect on carotid body tissue PO2 presumably because of its unusually high tissue blood flow. Six young male rats were exposed to 0.4-0.5 Torr (0.05-0.07%) inspired PCO in air for 22 days. Control rats (n = 6) were maintained under similar conditions except for CO exposure. After the exposure period the rats were anesthetized, blood was collected for hematocrit, and the carotid bodies were surgically exposed and fixed for electron microscopy and morphometry of type I and type II cells and capillary endothelium. Hematocrit was significantly greater in the CO-exposed group (75 vs. 48%), whereas no significant difference was found in the carotid body parenchyma between the control and CO-exposed groups. We conclude that the lack of an effect of chronic CO exposure on the carotid bodies in contrast to the strong erythropoietic response indicates a relatively high tissue blood flow rate in the carotid body and that CO did not exert a direct cellular effect. The results also suggest that the hypertrophic response of carotid body glomus cells to chronic hypoxic hypoxia is the result of a local direct effect of low PO2 rather than secondary to systemic effects.     

Cardiac output distribution and regional blood flow during hypocarbia in monkeys

Cardiac output distribution and regional blood flow were studied during hypocarbia independent of changes in ventilatory parameters. Fifteen cynomolgus monkeys were anesthetized with methohexital sodium (8 mg/kg im) and hyperventilated through an endotracheal tube. Hypocarbia at two levels, 28 +/- 1.8 and 17 +/- 0.6 Torr, was achieved by a stepwise decreasing CO2 flow into the semiclosed system. Regional blood flow was determined with labeled microspheres. At each stage of experiments two sets of microspheres (9 and 15 microns diam) were used simultaneously. The use of two microsphere sizes allowed evaluation of the relationship between total (nutritive and nonnutritive) tissue blood flow, determined with 15-microns spheres, and nutritive blood flow, determined with 9-microns spheres. There was no change in cardiac output or arterial pressure during both degrees of studied hypocarbia. Hypocarbia was accompanied by a decrease in myocardial blood flow determined with 15-microns spheres and preservation of the flow determined with 9-microns spheres. Splenic blood flow was decreased, whereas hepatic arterial blood flow was increased during both levels of hypocarbia. Blood flow through the brain, renal cortex, and gut showed a biphasic response to hypocarbia: during hypocarbia at 28 +/- 1.8 Torr, blood flow determined with 15-microns spheres was unchanged (in the gut) or decreased (in the brain and kidneys), whereas blood flow determined with 9-microns spheres was decreased. During hypocarbia at 17 +/- 0.6 Torr, blood flow determined with 9-microns spheres had a tendency to restore to base-line values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct assessment and distribution of regional portal blood flow in the pig by means of fluorescent microspheres.

Measurement of regional organ blood flow by means of fluorescent microspheres (FM) is an accepted method. However, determination of regional portal blood flow (RPBF) cannot be performed by microspheres owing to the entrapment of the spheres in the upstream capillary bed of the splanchnic organs. We hypothesized that an adequate experimental setting would enable us to measure RPBF by means of FM and to analyze its distribution within the pig liver. A mixing chamber for the injection of FM was developed, and its capability to distribute FM homogeneously in the blood was evaluated in vitro. The chamber was implanted into the portal vein of six anesthetized pigs (23.5 +/- 2.9 kg body wt). Three consecutive, simultaneous injections of FM of two different colors into the chamber were performed. Reference portal blood samples were collected by means of a Harvard pump. At the end of the experiment, the liver was explanted and fixed in formalin before dissection. FM were isolated from the tissue samples by an automated process, and fluorescence intensity was determined. Comparison of 5,458 single RPBF values, determined by simultaneously injected FM, revealed good agreement (bias 2.5%, precision 12.7%) and high correlation (r = 0.97, r2 = 0,95, slope = 1.04, intercept = 0.05). Median RPBF was 1.07 +/- 0.78 ml x min(-1) x g(-1). Allocation of the blood flow values to the anatomic regions of the liver revealed a significantly higher RPBF (P = 0.01) in the liver tissue located close to the diaphragm compared with the rest of the organ and a significantly lower RPBF (P = 0.01) in the left liver lobe compared with the median and right lobes. The results show that the model presented makes it possible to measure RPBF by means of FM reliably and that RPBF is distributed heterogeneously in the porcine liver.     

Regional measurement of canine skeletal muscle blood flow by positron emission tomography with H2(15)O.

Positron emission tomography (PET) with H2(15)O was used as an in vivo, relatively noninvasive, quantitative method for measuring regional blood flow to hindlimb skeletal muscle of anesthetized dogs. A hydrooccluder positioned on the femoral artery was used to reduce flow, and high-flow states were produced by local infusion of adenosine. Three to four measurements were made in each animal. Approximately 40 mCi of H2(15)O were injected intravenously, and serial images and arterial blood samples were acquired over 2.5 min. Data analysis was performed by fitting tissue and arterial blood time-activity curves to a modified, single-compartment Kety model. The model equation was also solved on a pixel-by-pixel basis to yield maps of regional skeletal muscle blood flow. After each PET determination, flow was measured with radioactive microspheres. Results of the PET measurements demonstrated that basal flow to hindlimb skeletal muscle was 3.83 +/- 0.36 ml x min(-1) x 100 g(-1) (mean +/- SE). This value was in excellent agreement with the microsphere data, 3.73 +/- 0.32 ml x min(-1) x 100 g(-1) (P = 0.69, not significant). Adenosine infusion resulted in flows as high as 30 ml x min(-1) x 100 g(-1), and the PET and microsphere data were highly correlated over the entire range of flows (r2 = 0.98, P < 0.0001). We conclude that muscle blood flow can be accurately measured in vivo by PET with H2(15)O and that this approach offers promise for application in human studies of muscle metabolism under varying pathophysiological states.     

Local blood flow velocities in the carotid body of fetal sheep and newborn lambs

Summary Elastically-suspended microelectrodes were used in the vascularly isolated blood-perfused carotid body of fetal and newborn lambs as well as of 6–7-day-old lambs to measure local blood flow velocities by means of hydrogen clearance. Fetal sheep (n=9) carotid bodies elicited mean local blood velocity values between 0.008 and 0.11 cm·s^–1, whereas newborn lamb carotid bodies (n=7) showed values between 0.008 and 0.067 cm·s^–1 at a perfusion pressure range between 30 and 150 mmHg. The 6–7-day-old lamb carotid bodies (n=5) were characterized by values of 0.003 and 0.049 cm·s^–1 over the same perfusion pressure range. Fetal carotid body values were statistically significantly higher than the values of the 6–7-day-old lamb carotid bodies, whereas the newborn carotid body values showed no significant difference to both other groups. The flow velocity/perfusion pressure relationship peaked at perfusion pressure values between 100 and 150 mmHg in all groups with a reduced steepness in the lamb carotid body. It is concluded that local blood flow velocities in the carotid body are similar to that in other organs, and that after birth local blood flow velocities in the carotid body decrease during the first week of life, probably induced by vasoconstriction, changed blood gas values, and/or increasing shunt flow.Abbreviations significance level - D diffusion coefficient - i.v. intravenous - n number of experiments - PCO ₂ carbon dioxide partial pressure - pH negative logarithm of hydrogen ion concentration - PH ₂ hydrogen partial pressure - Po PH₂ with perfusion - P PH₂ without perfusion - PO ₂ oxygen partial pressure - PP perfusion pressure - r radius     

High spatial resolution measurements of organ blood flow in small laboratory animals

With the use of a newly developed Imaging Cryomicrotome to determine the spatial location of fluorescent microspheres in organs, we validate and report our processing algorithms for measuring regional blood flow in small laboratory animals. Microspheres (15-microm diameter) of four different fluorescent colors and one radioactive label were simultaneously injected into the left ventricle of a pig. The heart and kidneys were dissected, and the numbers of fluorescent and radioactive microspheres were determined in 10 randomly selected pieces. All microsphere counts fell well within the 95% expected confidence limits as determined from the radioactive counts. Fluorescent microspheres (15-microm diameter) of four different colors were also injected into the tail vein of a rat and the left ventricle of a rabbit. After correction for Poisson noise, correlation coefficients between the colors were 0.99 +/- 0.02 (means +/- SD) for the rabbit heart and 0.99 +/- 0.02 for the rat lung. Mathematical dissection algorithms, statistics to analyze the spatial data, and methods to visualize blood flow distributions in small animal organs are presented.     

Evidence for a contribution by brown adipose tissue to the development of fever in the young rabbit

This study was undertaken to determine if brown adipose tissue was involved in heat production during fever produced by S. abortus equi (1 micrograms) in unanesthetized rabbits aged 19-26 days. The fever (0.9-1.6 degrees C) occurred after a delay of 20-30 min and was frequently biphasic. Radiolabelled microspheres for measuring tissue blood flow were injected intraventricularly into three groups of animals: rabbits not given pyrogen, rabbits in which the febrile response to pyrogen was developing, and rabbits in which the febrile response had peaked. Blood flow to brown fat deposits and other organs was calculated from the fractional distribution of the microspheres and the recovery of microspheres in a reference arterial blood sample. At the fever peak, blood flow to brown fat was not significantly different (p greater than 0.05) from the control value (0.9 +/- 0.2), but during the rising phase of the fever the flow increased significantly (p less than 0.01) to 2.6 +/- 0.4 mL min-1 g-1. The blood flow to muscles of the forelimbs and hind limbs was also increased significantly (p less than 0.05) during the rising phase of the fever. No significant change in blood flow to other organs or tissues was found during the rising phase of the fever. These results indicate that both nonshivering as well as shivering thermogenesis contribute to heat production during development of fever in the young rabbit. However, nonshivering thermogenesis was not involved in the maintenance of the elevated body temperature after the fever had peaked.     

The effect of labour on uterine blood flow in the pregnant ewe.

The effect of labour on cardiac output and uterine blood flow was measured in pregnant ewes at a mean gestation of 124 days using radioactive microspheres labelled with 169Yb and 85Sr. Labour was induced by a continuous infusion of ACTH into the foetal circulation. Cardiac ouput measured before ACTH infusion in seven ewes was 5234 +/- 175-9 ml./min (mean +/- S.E.) and total uterine blood flow was 732 +/- 57-9 ml./min (mean +/- S.E.). Measurements during labour in six ewes showed a significant increase in cardiac output to 6175 +/- 149-6 ml./min (P less than 0-005) but no significant change in uterine blood flow. However, the partition of blood flow was altered; thus myometrial flow increased by 67% from 114 +/- 15-4 ml./min to 190 +/- 13-2 ml./min (P less than 0-005) while placental blood flow decreased, although not significantly, from 618 +/- 55-9 ml./min to 575 +/- 40-7 ml./min. Similar changes were observed in one ewe in spontaneous labour at term and in another ewe receiving an infusion of 4 mg oestradiol 17beta over a 24 hr period. It is concluded that labour is not associated with any major alternation in total uterine blood flow although myometrial blood flow is increased. It is not known whether this is due to the rise in circulating oestrogens which occurs prior to parturition in the ewe, or to other factors such as the work of uterine muscle during labour.     

Regional heterogeneity of myocardial blood flow within the rabbit left ventricle during haemorrhagic hypotension.

Several studies have reported an extensive regional heterogeneity in myocardial blood flow. The reported coefficients of variation for regional myocardial perfusion range from about 0.2 to 0.4 in normotensive animals. The spatial distribution of myocardial perfusion during haemorrhagic hypotension seems not to have been assessed. The goal of the present study was to determine the regional heterogeneity in myocardial blood flow within the rabbit left ventricle during normal conditions and after haemorrhagic hypotension. Radioactive microspheres were infused into the left ventricle in barbiturate anaesthetized rabbits over either 30 or 120 sec. The haemorrhagic hypotension was induced by bleeding, so that mean arterial blood pressure was reduced to about 50% of control. The left ventricles were divided into samples of about 0.025 g each. Regional heterogeneity in the blood flow was expressed as the coefficient of variation corrected for the Poisson distribution of microspheres (CVc). The CVc was 0.37 +/- 0.09 (mean +/- SD) during control and 0.41 +/- 0.11 after bleeding, the CVc obtained after bleeding being somewhat higher than during control (P < 0.05). We obtained a high correlation coefficient (tau about 0.68) between regional perfusion values at control and after bleeding which indicates a stable perfusion pattern within the myocardium. We conclude that the regional distribution of coronary blood flow within the left ventricle is markedly heterogenous during control condition and that this pattern is not changed during haemorrhagic hypotension.     

Metabolic flux measurements across portal drained viscera, liver, kidney and hindquarter in mice

A method was developed to measure metabolic fluxes across either portally-drained viscera (PDV) and liver or kidney and hindquarter (HQ) in anesthetized mice. The method includes a primed-constant infusion of ketamine-medetomidine anaesthesia to stabilize the mice for the surgical procedures. For measurement of metabolic fluxes across PDV and liver, blood sampling catheters were inserted in the carotid artery, portal vein and hepatic vein and infusion catheters in the jugular vein and mesenteric vein. For measurement of metabolic flux across kidney and HQ, blood sampling catheters were inserted in the carotid artery, renal vein and caval vein and infusion catheters in the jugular vein and abdominal aorta. 14C-PAH was infused to enable plasma flow measurement using an indicator dilution method. In addition, we developed a blood sampling procedure without waste of blood. We measured plasma flow and metabolic fluxes across PDV, liver, kidney and HQ. Mean plasma flow in post-absorptive mice was: PDV: 0.9+/-0.2, liver: 1.2+/-0.3, kidney: 1.0+/-0.1, HQ: 1.1+/-0.3 ml/10 g body weight (b.w.)/min. Significant glutamine release by the HQ and uptake of glutamine by the kidney and PDV was observed. In PDV, citrulline is produced from glutamine and is in turn used by the kidney for the production of arginine. In conclusion, the described model enables measurement of metabolic fluxes across PDV, liver, kidney and HQ in mice. The availability of such a small animal model allows the potential for measuring metabolic parameters in transgenic and knockout mice, and therefore may lead to an important refinement in metabolic research.     

Relative influence of carotid baroreceptors and muscle receptors in the control of renal and hindlimb circulations.

In vagotomized dogs, a comparison was made of the relative ability of the carotid baroreceptors and of the receptors in skeletal muscles to cause constriction of the renal and hindlimb resistance vessels. With kidney and hindlimb perfused at constant pressure a decrease in pressure in the carotid sinuses from 250 to 40-45 mm Hg (1 mm Hg = 133 N/m2) caused the respective blood flows to increase by 19 +/- 6% and 80 +/- 4% (mean +/- SE), and stimulating muscle receptors with capsaicin caused a further decrease of 49 +/- 9% and 4 +/- 2%, respectively. With perfusion at constant flow, the baroreflex caused an increase of 34 +/- 4 mm Hg in the renal perfusion pressure and of 99 +/- 10 mm Hg in the hindlimb; capsaicin caused further increases of 203 +/- 17 and 35 +/- 9 mm Hg; respectively. These responses were abolished by sympathectomy. Capsaicin injection increased mean renal sympathetic nerve activity by 111 +/- 16% over the maximal impulse frequency recorded when the carotid sinus pressure was 40-45 mm Hg. Thus, withdrawal of the restraint exerted by the carotid baroreceptors on the pool of central neurons controlling the vascular beds of the hindlimb and kidney leads to near maximal constriction of the resistance vessels in the former bu not the latter; with strong activation of muscle receptors, near maximal constriction occurs in both beds.     

Systemic blood flow to sheep lung: comparison of flow probes and microspheres.

Discrepancies exist between experimental measurements of the systemic blood flow to sheep lung by use of microsphere techniques and flow probes on the bronchial artery. In these studies, we simultaneously measured the blood flow through the bronchial artery, using a transit time flow probe, and the systemic blood flow to left lung, using radioactive microspheres. All measurements were made on conscious sheep previously prepared with chronic catheterizations of the left atrium, aorta, and vena cava and a flow probe around the bronchial artery. Inflatable occluder cuffs were placed around the pulmonary and bronchoesophageal arteries. Bronchial artery blood flow in six sheep was 25.3 +/- 5.2 ml/min or 0.4% of the cardiac output. Systemic blood flow to left lung, measured with microspheres, was 54.1 +/- 14.2 ml/min. Calculated systemic blood flow to that portion of sheep lung perfused by the bronchial artery was 127.6 +/- 35.3 ml/min or 1.9% of cardiac output. Occlusion of the bronchoesophageal artery reduced bronchial artery flow to near zero, whereas total systemic blood to the lung was reduced by only 55%. Blood flow to the intraparenchymal cartilaginous airways was reduced 60-90% after occlusion of the bronchoesophageal artery. Sheep, like most mammals, have multiple and complex systemic arterial inputs to the lungs. We conclude that multiple branches of the bronchoesophageal artery provide most but not all of the systemic blood flow to the intraparenchymal cartilaginous airways but that over one-half of the total systemic blood flow to sheep lung comes from sources other than the common bronchial artery.     

Myocardial O2 consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O2 delivery

Myocardial blood flow is unevenly distributed, but the cause of this heterogeneity is unknown. Heterogeneous blood flow may reflect heterogeneity of oxygen demand. The aim of the present study was to assess the relation between oxygen consumption and blood flow in small tissue regions in porcine left ventricle. In seven male, anesthetized, open-chest pigs, local oxygen consumption was quantitated by computational model analysis of the incorporation of 13C in glutamate via the tricarboxylic acid cycle during timed infusion of [13C]acetate into the left anterior descending coronary artery. Blood flow was measured with radioactive microspheres before and during acetate infusion. High-resolution nuclear magnetic resonance 13C spectra were obtained from extracts of tissue samples (159 mg mean dry wt) taken at the end of the acetate infusion. Mean regional myocardial blood flow was stable [5.0 +/- 1.6 (SD) and 5.0 +/- 1.4 ml.min(-1).g dry wt(-1) before and after 30 min of acetate infusion, respectively]. Mean left ventricular oxygen consumption measured with the NMR method was 18.6 +/- 7.7 micromol.min(-1).g dry wt(-1) and correlated well (r = 0.85, P = 0.02, n = 7) with oxygen consumption calculated from blood flow, hemoglobin, and blood gas measurements (mean 22.8 +/- 4.7 micromol.min(-1).g dry wt(-1)). Local blood flow and oxygen consumption were significantly correlated (r = 0.63 for pooled normalized data, P < 0.0001, n = 60). We calculate that, in the heart at normal workload, the variance of left ventricular oxygen delivery at submilliliter resolution is explained for 43% by heterogeneity in oxygen demand.