Angio-Based Index of Microcirculatory Resistance for the Assessment of the Coronary Resistance: A Proof of Concept Study.

BACKGROUND: The study of coronary microcirculation has gained increasing consideration and importance in cath lab. Despite the increase of evidence, its use still remains very limited. QFR is a novel angio-based approach for the evaluation of coronary stenosis. The aim of our study was to use the QFR assessment in stable patients to recreate the IMR formula and to correlate the result of the two techniques. METHODS: From June 1, 2019, to February 29, 2019, 200 patients with CCS and indication of coronary artery angiography and referred to the cath lab of the University Hospital of Ferrara (Italy) were enrolled. After baseline coronary angiogram, quantitative flow ratio, fractional flow reserve, and index of microcirculatory resistance evaluation were performed. RESULTS: Pearson correlation (r) between angio-based index of microcirculatory resistance (A-IMR) and IMR 0.32 with R 2 = 0.098, P=0.03: McNemar test showed a difference between the two tests of 6.82% with 95% CI from -12.05% to 22.89%, which is not significant (P=0.60). Bland and Altman plot showed a mean difference of 23.3 (from -26.5 to 73.1). Sensitivity, specificity, NPV, and PPV were 70%, 83.3%, 75%, and 70% for A-IMR value >44.2. The area under the ROC curve for A-IMR was 0.76 (95% CI 0.61-0.88, P=0.0003). CONCLUSION: We have validated for the first time the formula of the A-IMR, a tool for the calculation of microvascular resistance which does not require the use of pressure guides and the induction of hyperemia.

Effects of Foam Microbubbles on Electrical Resistivity and Capillary Pressure of Partially Saturated Porous Media.

Laboratory measurements of capillary pressure (Pc) and the electrical resistivity index (RI) of reservoir rocks are used to calibrate well logging tools and to determine reservoir fluid distribution. Significant studies on the methods and factors affecting these measurements in rocks containing oil, gas, and water are adequately reported in the literature. However, with the advent of chemical enhanced oil recovery (EOR) methods, surfactants are mixed with injection fluids to generate foam to enhance the gas injection process. Foam is a complex and non-Newtonian fluid whose behavior in porous media is different from conventional reservoir fluids. As a result, the effect of foam on Pc and the reliability of using known rock models such as the Archie equation to fit experimental resistivity data in rocks containing foam are yet to be ascertained. In this study, we investigated the effect of foam on the behavior of both Pc and RI curves in sandstone and carbonate rocks using both porous plate and two-pole resistivity methods at ambient temperature. Our results consistently showed that for a given water saturation (Sw), the RI of a rock increases in the presence of foam than without foam. We found that, below a critical Sw, the resistivity of a rock containing foam continues to rise rapidly. We argue, based on knowledge of foam behavior in porous media, that this critical Sw represents the regime where the foam texture begins to become finer, and it is dependent on the properties of the rock and the foam. Nonetheless, the Archie model fits the experimental data of the rocks but with resulting saturation exponents that are higher than conventional gas-water rock systems. The degree of variation in the saturation exponents between the two fluid systems also depends on the rock and fluid properties. A theory is presented to explain this phenomenon. We also found that foam affects the saturation exponent in a similar way as oil-wet rocks in the sense that they decrease the cross-sectional area of water available in the pores for current flow. Foam appears to have competing and opposite effects caused by the presence of clay, micropores, and conducting minerals, which tend to lower the saturation exponent at low Sw. Finally, the Pc curve is consistently lower in foam than without foam for the same Sw.

Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation.

BACKGROUND: The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE cell morphology and key functions in vitro. METHODS: Primary porcine RPE cells were exposed to TNFα (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE cell morphology, phagocytosis, barrier- and immunosuppressive-functions were assessed. RESULTS: Chronic (10 days) exposure of primary RPE cells to TNFα increases RPE cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNFα-induced morphological- and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor ß inhibition. CONCLUSIONS: Our results indicate that chronic TNFα-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration.

Capillary refill time is a predictor of short-term mortality for adult patients admitted to a medical department: an observational cohort study.

BACKGROUND: Capillary refill time (CRT) has been advocated as a tool for rapid assessment of circulatory status. The correlation between neither CRT and mortality nor CRT and markers of circulatory status has been assessed. We performed a prospective observational cohort study to assess the relationship between CRT (using two existing definitions and as a continuous variable) and short-term mortality. METHODS: We included all acutely admitted adult patients to a medical admission unit. We measured CRT, blood pressure, pulse, temperature and peripheral oxygen saturation. We presented the data descriptively. Difference between continuous data was analysed using Wilcoxon Rank Sum Test and categorical data using χ(2) test. The primary endpoint was 1-day all-cause mortality. RESULTS: 3046 patients were enrolled and CRT was measured on 1935. In univariate analyses, we found increasing all-cause 1-day mortality with all definitions of CRT. Performing multivariable analysis, controlling for age, sex, mean blood pressure, pulse, temperature and peripheral oxygen saturation, we found increasing CRT as a continuous variable and according to the Schriger and Baraff definition to be associated with increased mortality. Both the Trauma score and Schriger and Baraff definitions had high negative predictive values. The calculations on the Schriger and Baraff definition were based on limited power. CONCLUSIONS: We found a significant association between CRT measured as a continuous variable and short-term mortality. Using the definition of Schriger and Baraff also seems appropriate, but this is based on calculations of limited power.

Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold videocapillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. METHODS: Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (≥35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. RESULTS: An NVC score >1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade >1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). CONCLUSION: Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated.

[Optimization approach to arterial hemodynamics in elastic capillaries].

The article considers a number of ways of optimizing arterial hemodynamics including finding of the best value of capillary resistance or coefficient of elasticity.

Pharmacological treatment of primary chronic venous disease: rationale, results and unanswered questions.

AIM: The aim of this article was first to review the complex pathophysiological mechanisms responsible for symptoms and signs of primary chronic venous disease (CVD) that allow the identification of targets for pharmacological treatment. The results of CVD treatment with venoactive drugs (VADs) were emphasised and presented in the form of recommendations. The last section raises key questions to be answered to improve protocols for good clinical trials and to draw up future guidelines on these agents. METHODS: The literature has been reviewed here using PubMed and Embase. RESULTS: Venous hypertension appears to underlie all clinical manifestations of primary CVD. Inflammation is key in wall remodelling, valve failure and subsequent venous hypertension. Changes in the haemodynamics of veins are transmitted to the microcirculation, resulting in capillary alteration leading to oedema, skin changes and eventually venous ulceration. Venous symptoms may be the result of interplays between pro-inflammatory mediators and nerve fibres located in the venous wall. Therefore, venous inflammation constitutes a promising therapeutic target for pharmacological intervention, and some available VADs could attenuate various elements of venous inflammation. Based on recent studies, reviews and guidelines, tentative recommendations for the use of VADs were proposed and strong recommendations were given to two of them (micronised purified flavonoid fraction and oxerutins). CONCLUSION: VADs should be accorded a better role in the management of CVD. However, larger and more definitive clinical trials are needed to improve the existing recommendations.

The two layer method does not improve the preservation of porcine kidneys.

BACKGROUND: The Two layer method (TLM) has been extremely successful in the preservation of the pancreas. However, this has not been thoroughly investigated in other organs or in clinically relevant large animal models. The aim of this study was to assess the effects of TLM in a large animal model of kidney preservation. MATERIAL/METHODS: Porcine kidneys were retrieved after 10 minutes of warm ischaemic injury and flushed with 300 ml UW solution at 4°C. Kidneys were then either placed in University of Wisconsin solution (UW) or TLM using pre-oxygenated perfluorodecalin and UW. Kidneys were stored for 18 hours at 4°C then reperfused with oxygenated autologous blood to assess renal function. RESULTS: Renal blood flow (RBF) was significantly lower and intra-renal resistance (IRR) higher in TLM compared to UW group [Area under the curve (AUC) RBF, UW; 427±168 vs TLM; 247±55 ml/min/100g.h; P=0.041, AUC IRR, UW; 7.7±2.2 vs TLM; 10.5±1.9 ml/min/mmHg; P=0.041]. Levels of creatinine clearance (CrCl) were significantly lower in TLM group [AUC CrCl, UW; 1.8±1.0 vs TLM; 0.6±0.4 ml/min/100 g.h; P=0.034]. Levels of lipid peroxidation were significantly lower in TLM group [8-isoprostane/Cr ratio 3h; UW 3338±896 vs TLM 2072±886 pg/ml/mmol/L; P=0.04]. Levels of total nitric oxide were significantly higher in TLM group (P=0.009). CONCLUSIONS: TLM did not improve the preservation condition of porcine kidneys. Furthermore, there appeared to be increased inflammation, endothelial injury and reduced renal function compared to preservation with UW. Further experimental work is needed to determine the role of PFC in kidney preservation.

Intracoronary streptokinase after primary percutaneous coronary intervention.

BACKGROUND: Microvascular perfusion is often impaired after primary percutaneous coronary intervention (PCI). We proposed that in situ thrombosis might contribute to poor myocardial perfusion in this setting. To test this hypothesis, we evaluated the effect of low-dose intracoronary streptokinase administered immediately after primary PCI. METHODS: Forty-one patients undergoing primary PCI were randomly assigned to receive intracoronary streptokinase (250 kU) or no additional therapy. Two days later, cardiac catheterization was repeated, and coronary hemodynamic end points were measured with the use of a guidewire tipped with pressure and temperature sensors. In patients with anterior myocardial infarction, the deceleration time of coronary diastolic flow was measured with transthoracic echocardiography. At 6 months, angiography, echocardiography, and technetium-99m single-photon-emission computed tomography were performed. RESULTS: Two days after PCI, all measures of microvascular function (means +/-SD) were significantly better in the streptokinase group than in the control group, including coronary flow reserve (2.01+/-0.57 vs. 1.39+/-0.31), the index of microvascular resistance (16.29+/-5.06 U vs. 32.49+/-11.04 U), the collateral-flow index (0.08+/-0.05 vs. 0.17+/-0.07), mean coronary wedge pressure (10.81+/-5.46 mm Hg vs. 17.20+/-7.93 mm Hg), systolic coronary wedge pressure (18.24+/-6.07 mm Hg vs. 33.80+/-11.00 mm Hg), and diastolic deceleration time (828+/-258 msec vs. 360+/-292 msec). The administration of intracoronary streptokinase was also associated with a significantly lower corrected Thrombolysis in Myocardial Infarction frame count (the number of cine frames required for dye to travel from the ostium of a coronary artery to a standardized distal coronary landmark) at 2 days. At 6 months, however, there was no evidence of a difference between the two study groups in left ventricular size or function. CONCLUSIONS: In our pilot trial, the administration of low-dose intracoronary streptokinase immediately after primary PCI improved myocardial reperfusion but not long-term left ventricular size or function. These findings require clarification in a larger trial. (ClinicalTrials.gov number, NCT00302419.)

Pulsatile stress correlates with (micro-)albuminuria in renal transplant recipients.

Pulsatile stress is defined as product of pulse pressure (PP) and heart rate (HR) and is largely regulated by arterial stiffness in general and specifically with reference to patients with renal insufficiency by sympathetic nerve activity. Direct effects of the pulsatile stress on heart, coronary system and ultimately cardiovascular survival have been documented whereas no data exist relating to renal transplant patients. We analysed the relation of macrocirculatory disturbance to microcirculatory defects in 92 renal transplant recipients. Therefore, we investigated aortic stiffness by carotid-femoral pulse wave velocity (PWV), pulsatile stress and albuminuria. Pulsatile stress, not PWV was associated with the extent of albuminuria (r = 0.29; P < 0.01 and r = 0.06; P = 0.6 respectively), which was confirmed in multivariate stepwise regression analysis (P = 0.008). Dividing the data in tertiles of pulsatile stress revealed an eightfold increased risk for microalbuminuria and 12.2-fold increased risk for macroalbuminuria comparing upper with lower tertile of pulsatile stress. Pulsatile stress, not PWV correlates with albuminuria and predicts the degree of albuminuria in renal transplant recipients. Therefore, pulsatile stress reflects an easy and cost-effective marker for renal microcirculatory defects in renal transplant patients.

Intermittent versus constant aerobic exercise: effects on arterial stiffness.

Aerobic exercises (of sufficient duration and intensity) decreases arterial stiffness. However, the direct relationship between the type of aerobic exercise (i.e. constant versus interval) and the alteration in arterial stiffness has been poorly explored. We evaluated the hemodynamic responses of 11 healthy males (22.5 +/- 0.7 years, height 177.7 +/- 1.1 cm, body mass 70.5 +/- 2.4 kg) following acute constant (CE) and intermittent cycling exercise (IE). Exercise duration and intensity (mean heart rate) were matched during both exercises (142.9 +/- 2.4 bpm for CE and 144.2 +/- 2.4 bpm for IE). Heart rate (HR) and cardiac output (CO) were measured throughout the whole session, while blood pressure and pulse wave velocity (PWV) were measured during pre exercise and 30 min recovery. Arterial stiffness and cardiac autonomic control were assessed through PWV and heart rate variability, respectively. After IE, lower limb arterial stiffness was significantly and steadily decreased compared to pre exercise value (from 8.6 +/- 0.1 to m s(-1) to 7.6 +/- 0.3 to m s(-1) at 30 min) and was lower than after CE (8.2 +/- 0.3 m s(-1) at 30 min, which did not significantly change compared to pre exercise: 8.7 +/- 0.2 m s(-1)). We hypothesized that the higher HR and lower arterial stiffness after IE were likely due to variations in peripheral vascular changes during the exercise which may trigger the release of endothelial or metabolic vasoactive factors. These data appear to show that IE may result in a greater stimulus for vascular adaptations when compared to CE.

Association of Hyperhomocysteinemia with Increased Coronary Microcirculatory Resistance and Poor Short-Term Prognosis of Patients with Acute Myocardial Infarction after Elective Percutaneous Coronary Intervention.

BACKGROUND: This study aims to investigate the coronary microcirculatory resistance and prognosis of patients with acute myocardial infarction (AMI) concomitant with hyperhomocysteinemia (HHcy) after an elective percutaneous coronary intervention (PCI). METHODS: A total of 101 patients that underwent elective PCI between May 2015 and July 2018 due to AMI were consecutively enrolled in this study. Patients were divided into a HHcy group (53) and a normal Hcy group (control; 48) based on their plasma homocysteine concentration. The characteristics of coronary angiography, the index of microcirculatory resistance (IMR) of infarct-related vessels (IRV), changes in left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) before and after PCI, and the incidence of major adverse cardiovascular events (MACE) three months after PCI were compared between these groups. RESULTS: Compared to the results from the Hcy group, the HHcy group had a higher IMR. The HHcy group had significantly higher LVEDd and a lower LVEF than the Hcy group 3 months after PCI. Additionally, the incidence of MACE at three months after PCI was higher in the HHcy group than in the Hcy group. Pearson correlation analysis revealed a positive correlation with IMR in the HHcy group. Furthermore, there was a difference in the LVEDd measured at one day after PCI and at three months after PCI in the HHcy group. CONCLUSION: AMI patients concomitant with HHcy that undergo elective PCI are prone to coronary microcirculatory dysfunction and have a poor cardiac function and poor prognosis at three months after PCI.

Why do red blood cells have asymmetric shapes even in a symmetric flow?

Understanding why red blood cells (RBCs) move with an asymmetric shape (slipperlike shape) in small blood vessels is a long-standing puzzle in blood circulatory research. By considering a vesicle (a model system for RBCs), we discovered that the slipper shape results from a loss in stability of the symmetric shape. It is shown that the adoption of a slipper shape causes a significant decrease in the velocity difference between the cell and the imposed flow, thus providing higher flow efficiency for RBCs. Higher membrane rigidity leads to a dramatic change in the slipper morphology, thus offering a potential diagnostic tool for cell pathologies.

[Total non-elastic pulmonary resistance and permeability of the alveolar capillary membrane in community-acquired pneumonia].

AIM: To study alveolar capillary membrane permeability (ACMP) and total non-elastic pulmonary resistance (TNPR) in patients with community-acquired pneumonia (CAP) in an acute period. MATERIAL AND METHODS: ACMP of the lungs was studied in 35 CAP patients with ventilation pulmonoscintigraphy. Integral and regional TNPR were registered at inhalation and expiration. Integral TNPR was estimated by simultaneous registration of transpulmonal pressure and spirogram, regional TNPR (in the upper, middle and lower zones of the lungs)--by simultaneous registration of zonal rheograms of ventilation and transpulmonal pressure. Bronchial resistance was measured by body plethismograph (Masterlab pro, Erich Jaeger, Germany). RESULTS: In acute CAP integral TNPR rose while regional values varied. Both integral and regional ACMP for affected and intact lungs were significantly elevated showing systemic impairment of the structures of alveolar-capillary membrane of the lungs. More severe alterations of integral ACMP were seen in the affected lung, of regional--in the affected zones. CONCLUSION: Changes registered in regional TNPR and ACMP may indicate enhanced mechanical activity of the lungs in these zones. This enhanced activity contributes to TNPR overcoming.

Minimal distensibility of pulmonary capillaries in avian lungs compared with mammalian lungs.

Previous physiological studies suggest that avian pulmonary capillaries behave like almost rigid tubes. We made morphometric measurements to determine the diameter of the capillaries in chicken lungs when the transmural pressure was altered over a wide range. The diameter of avian pulmonary capillaries increased by only 13% when the pressure inside them was raised from 0 to 25 cmH(2)O. In contrast, other studies have shown that the mean width of the pulmonary capillaries in dogs increased by about 125% and in cats by 128% for the same pressure change. Furthermore, raising the pressure 35 cmH(2)O outside the capillaries compared to the pressure inside the capillaries in chicken lungs caused little change in diameter whereas under the same conditions in mammal lungs the capillaries are completely collapsed. We conclude that the epithelial bridges between the blood capillaries in the bird lung provide strong support to the capillaries both in expansion and compression.

Relationship between electrocardiographic RR and QT interval variabilities and indices of ventricular function in healthy subjects.

To date there has been no simultaneous characterization of the influence of physical exercise on cardiac ventricular function and cardiac electrical variability. Consequently, little is known about the relationship between the ventricular function and either heart rate (RR) or repolarization (QT) variability. In particular, the relationship between the QT variability index (QTVI) and ventricular function would be of clinical interest. Eight males of similar age (20.7 +/- 0.4 years (mean +/- SD)), mass (78.4 +/- 7.7 kg) and aerobic fitness (50.7 +/- 4.9 ml kg(-1) min(-1)) undertook progressive bicycle exercise. A three-lead Holter ECG was recorded continuously during pre-exercise, exercise and recovery, and mean values of RR and QT, their variabilities (RMSSD and SDNN) and their relative variability (QTVI) were determined. Traditional indices of ventricular function were determined beat to beat via impedance cardiography, and beat-to-beat blood pressure was recorded via photoplethysmography. Multiple linear regression analysis using the stepwise method resulted in significant models for each of the dependent variables (RR, QT, RR and QT variabilities, QTVI), using indices of the ventricular function as predictor variables. Notably, the QTVI reflected both the stroke volume index (SVI) and the acceleration index (ACI), which are measures of cardiac 'output' per contraction and the force of contraction, respectively. This relationship was largely unperturbed by physical exercise, in contrast with the results for all other dependent variables. We conclude that the QTVI is a reasonably consistent measure of the cardiac ventricular function, and as such is a more useful index than other parameters based on RR or QT interval alone.

Clinical and coronary haemodynamic determinants of recurrent chest pain in patients without obstructive coronary artery disease - A pilot study.

BACKGROUND: Coronary haemodynamic testing frequently identifies abnormal pathophysiological parameters in patients with angina and non-obstructed coronaries on angiography (NoCAD) but the clinical utility of these measures has received limited attention. OBJECTIVE: This study aims to identify the clinical and coronary haemodynamic determinants of recurrent chest pain at one month in patients with NoCAD. METHODS: Patients with angina, NoCAD (<50% stenosis) and normal LV systolic function underwent invasive coronary haemodynamic testing involving: (1) angiographic TIMI frame and opacification rate, (2) microvascular functional measures including coronary flow reserve (CFR) and hyperaemic microvascular resistance (HMR), (3) coronary endothelial function assessment with low dose intracoronary acetylcholine (IC-ACh) infusions (0.18 µg/min & 1.8 µg/min over 2 min), and (4) Provocative spasm testing with high dose IC-ACh boluses (25, 50 and 100 µg). Clinical and health status were assessed at baseline and one month. RESULTS: In the 49 NoCAD patients (78% female, mean age of 54 ±â€¯11) undergoing comprehensive coronary haemodynamic testing, 33 (67%) continued to experience chest pain at one month. Determinants of recurrent chest pain on univariate analysis included baseline chest pain status or a HMR > 1.9. Multivariate logistic regression analysis identified frequent angina at baseline (OR: 68.9 [4.1, 1165.0], p = 0.003), previous unstable angina admission (OR: 43.9 [3.5, 547.9], p = 0.003) and a HMR > 1.9 (OR: 15.6 [2.1, 114.0], p = 0.007) as independent predictors of recurrent chest pain. CONCLUSION: In this small pilot study, an abnormal HMR was the only coronary haemodynamic parameter that was a determinant of ongoing angina at short-term follow-up.

Plasma catecholamines in long-term diabetics with and without neuropathy and in hypophysectomized subjects.

Employing a precise and sensitive double-isotope derivative technique, plasma catecholamine concentration (PCA) was measured in four groups of subjects: (a) long-term diabetics with neuropathy, (b) long-term diabetics without neuropathy, (c) hypophysectomized long-term diabetics with neuropathy, and (d) nondiabetic control subjects. Blood samples were obtained from subjects in the supine and in the standing position. In nondiabetic control subjects, PCA (mainly noradrenaline) increased from 0.26 ng/ml in the supine positon to 0.69 and 0.72 ng/ml 5 and 10 min after assuming the standing position. By plotting this increase in PCA on the y axis in a coordinate system vs. increase in pulse rate, PCA was divided into two components: one of these depended on the rise in pulse rate on standing (called CAH) and the other corresponded to the intercept on the y axis where rise in pulse rate equals zero (CAP).Long-term diabetics with neuropathy showed a significant reduction in PCA in both the supine and the standing position. Further analysis demonstrated that CAP was considerably reduced whereas CAH was normal. Long-term diabetics without neuropahty showed normal PCA values.Surprisingly, hypophysectomized diabetics with neuropathy exhibited mean PCA values in both the supine and the standing position which were similar to those found in the nondiabetic subjects and considerably elevated compared with the findings in the nonoperated, long-term diabetics with neuropathy. Further analysis in terms of CAP and CAH demonstrated, however, that CAP was just as abnormally reduced in the hypophysectomized as it was in the nonoperated patients whereas CAH was considerably increased. In contrast to the findings in the nonoperated diabetics with neuropathy, the hypophysectomized diabetic patients with neuropathy demonstrated a negative correlation between rise in PCA and blood pressure on standing indicating that the increase in PCA was at least partially a compensatory phenomenon in the interest of the maintenance of a normal level of blood pressure. An increased sympathetic tone (vasoconstriction) is believed to be at least partially responsible for the increased capillary resistance and decreased capillary permeability occuring after hypophysectomy.

Differential reactivity in the pulmonary circulation.

A new method for relating regional intravascular resistance to pulmonary arterial, capillary, and venous pressure and volume was used to evaluate local differences of reactivity in the pulmonary blood vessels in the isolated lung lobe of the dog. Intravascular infusion of isoproterenol caused active dilatation of pulmonary arteries and veins. Capillary conductance (1/resistance) and volume increased, possibly as a result of the opening of previously closed capillaries. Serotonin infusion caused active constriction of both the pulmonary arteries and veins. A low dose of serotonin (1.5 mug/min per kg) caused predominant constriction of whichever vessels were upstream (arteries during forward perfusion, veins during reverse perfusion). A high dose of serotonin (4.5-5.0 mug/min per kg) caused constriction of both upstream and downstream vessels. Metabolic inactivation of serotonin by the lung is suggested as an explanation for these observations. Histamine infusion caused predominant venous constriction whether veins were upstream or downstream. Capillary volume and conductance decreased during forward and reverse perfusion, perhaps as a result of pericapillary edema formation. Large arterial vessels constricted slightly, whereas small arterial vessels appeared to be passively dilated.

Major differences in the pulmonary circulation between birds and mammals.

The lungs of domestic chickens were perfused with blood or dextran/saline and the pulmonary artery pressure (P(a)) and venous pressure (P(v)) were varied in relation to air capillary pressure (P(A)). In Zone 3 conditions, pulmonary vascular resistance (PVR) was virtually unchanged with increases in either P(a) or P(v). This is very different behavior from mammals where the same interventions greatly reduce PVR. In Zone 2 conditions blood flow was essentially independent of P(v) as in mammalian lungs but all the capillaries appeared to be open, apparently incompatible with a Starling resistor mechanism. In Zone 1 the capillaries were open even when P(A) exceeded P(a) by over 30 cm H(2)O which is very different behavior from that of the mammalian lung. We conclude that the air capillaries that surround the blood capillaries provide rigid support in both compression and expansion of the vessels. The work suggests a pathogenesis for pulmonary hypertension syndrome in chickens which costs the broiler industry $1 billion per year.