Fall In Pa Research Articles

Hemodynamic Response to Intravenous Adenosine and Its Effect on Fractional Flow Reserve Assessment

We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both ΔPa and ΔPd were decreased (ΔPa, -10.2±10.5 mm Hg; ΔPd, -18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, -12.9±15.7 mm Hg; P<0.001; r=0.9; P<0.001). ΔPa and ΔPd were closely related under conditions of peak (r=0.75; P<0.001) and stable hyperemia (r=0.83; P<0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ≤0.80 and 5.2% with FFR threshold <0.75 when comparing Pd/Pa at peak and stable hyperemia. Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher.

Calcitonin gene‐related peptide contributes to the umbilical haemodynamic defence response to acute hypoxaemia

Despite clinical advances in obstetric practice, undiagnosed fetal hypoxaemia still contributes to a high incidence of perinatal morbidity. The fetal defence to hypoxaemia involves a redistribution of blood flow away from peripheral circulations towards essential vascular beds, such as the umbilical, cerebral, myocardial and adrenal circulations. In marked contrast to other essential vascular beds, the mechanisms mediating maintained perfusion of the umbilical circulation during hypoxaemia remain unknown. This study determined the role of calcitonin gene-related peptide (CGRP) in the maintenance of umbilical blood flow during basal and hypoxaemic conditions. Under anaesthesia, five sheep fetuses were instrumented with catheters and a Transonic probe around an umbilical artery, inside the fetal abdomen, at 0.8 of gestation. Five days later, fetuses were subjected to 0.5 h hypoxaemia during either i.v. saline or a selective CGRP antagonist in randomised order. Treatment started 30 min before hypoxaemia and ran continuously until the end of the challenge. The CGRP antagonist did not alter basal blood gas or cardiovascular status in the fetus. A similar fall in Pa,O2 occurred in fetuses during either saline (21 +/- 0.8 to 9 +/- 0.9 mmHg) or antagonist treatment (20 +/- 0.9 to 9 +/- 1.2 mmHg). Hypoxaemia during saline led to significant increases in arterial blood pressure, umbilical blood flow and umbilical vascular conductance. In marked contrast, hypoxaemia during CGRP antagonist treatment led to pronounced falls in both umbilical blood flow and umbilical vascular conductance without affecting the magnitude of the hypertensive response. In conclusion, CGRP plays an important role in the umbilical haemodynamic defence response to hypoxaemia in the late gestation fetus.

Measurements of mean systemic filling pressure in normal subjects during general anesthesia

Mean systemic filling pressure (Psf) is identified as the equilibrium pressure in the systemic circulation when the blood flow is zero. Psf might be an index of the effective filling of the circulatory system [1,2]. Aim of this study was to test a simple method to measure Psf in a population of anesthetized patients under conditions of intact circulation and during mechanical ventilation. Modeling the systemic circulation as a pipe of constant resistance we have assumed the venous return (Qv) to be proportional to the difference between arterial pressure (Pa) and central venous pressure (Pcv). According to Guyton's venous return equation: Qv = (Psf-Pcv)/Rsf. Rsf.d. is the resistance downstream to the site in the circulation where blood pressure is equal to Psf. For the systemic flow, Qs = (Pa–Psf)/Rsf.u (where Qs is the cardiac output and Rsf.u is the resistance upstream). Since Qv = Qs, then Pa = Psf+(1+Rsf.u/Rsf.d)-(Rsf.u/Rsf.d) × Pcv. If Rsf.u. Rsf.d and Psf are constant [2], then Pa is linearly related to Pcv, and Psf can be computed from the regression line Pa versus Pcv, at Pa = Pcv. In eight patients undergoing elective surgery (ASA I-II, weight 68.8 ± 12 kg, age 59.5 ± 14 years), with no previous history of cardiovascular and pulmonary diseases, anesthesia was induced by pentobarbital and maintained with isofluorane (0.4%) and nitrous oxide, while neuromuscular blocking agents were atracurium or pancuronium bromide. The averaged hemodynamic baseline was: HR 85.2 ± 21.6 bpm; Pa 84.6 ± 13.8 mmHg: Pcv 5.26 ± 2.08 mmHg. Airway pressure, flow, Pa and Pcv traces were simultaneously measured, recorded and digitalized on a data acquisition system (Colligo, Elekton, Italy). In order to induce changes in Pcv and consequently in Qv, at least five end inspiratory pauses (IP) were performed after inflation of different tidal volumes (Vt), applied in a random order. The Vt ranged from 8.2 ± 2 ml/kg to 26.0 ± 10 ml/kg. We have measured the fall in Pa and the rise in Pcv caused by IP. At each step Pcv and Pa were measured during the IP, when the fall in Pa reached a plateau, ie after a mean time of 9.1 ± 3.7 s.

Effect of vascular puncture on blood gases in the Newborn

Continuous monitoring methods have shown changes of oxygenation in neonates during various procedures. However, actual changes in blood gases during vascular punctures have not been reported. We studied the effect of vascular puncture on arterial blood gases during routine venipuncture in 17 neonates who had indwelling arterial catheters. Arterial blood gases were analyzed before, during, and following recovery from venipuncture. Ventilator settings were not changed during the study, though oxygen concentration (FiO2) was adjusted as indicated by continuous PO2 or saturation monitors. During venipuncture, there was a significant fall in PaCO2 from 38 +/- 5 to 32 +/- 7 mmHg (P less than 0.0001) and in PaO2 from 75 +/- 21 to 58 +/- 23 mmHg (P less than 0.0001). Following venipuncture, both values returned to baseline. The results of this study imply that blood gases obtained by intermittent arterial sticks may provide data that do not accurately reflect the neonates' respiratory status.

Influences on the cardiovascular response to graded levels of systemic hypoxia of the accompanying hypocapnia in the rat.

1. In spontaneously breathing, anaesthetized rats, a study was made of the effects upon the graded cardiovascular responses to systemic hypoxia (inspiratory fractional O2 concentration, Fi, O2: 0.15, 0.12, 0.08, 0.06) of maintaining arterial CO2 pressure (Pa,CO2) at the air-breathing level by adding CO2 to the inspirate (eucapnic hypoxia), rather than allowing Pa,CO2 to fall (hypocapnia hypoxia). 2. At each Fi,O2, maintenance of eucapnia significantly reduced the increase in respiratory frequency, but significantly accentuated the increase in tidal and minute volume: as a result the fall in Pa,O2 at each Fi,O2 was significantly reduced. 3. Concomitantly, maintenance of eucapnia reduced the increase in heart rate (HR) and fall in arterial pressure (ABP), the effects being significant at Fi,O2 0.08 and/or 0.06. There was also a tendency for the increases in renal and femoral vascular conductances (RVC, FVC) to be reduced; at Fi,O2 0.06 mean increases from control were 2 +/- 10 vs. 16 +/- 7% (eucapnia vs. hypocapnia) for RVC, and 62 +/- 11 vs. 106 +/- 27% for FVC. 4. As maintenance of eucapnia reduced the fall in Pa,O2 at each Fi,O2, the above results were also considered as a function of Pa,O2. Then, maintenance of eucapnia had similar significant effects on the changes in respiration and HR as described above and reduced the mean increase in RVC (16 +/- 11 vs. 23 +/- 10%, at Pa,O2 31 mmHg, which was attained at Fi,O2 0.06 with eucapnia and 0.08 with hypocapnia). However, maintenance of eucapnia had no effect on the falls in ABP and accentuated the mean increase in FVC (74.9 +/- 13 vs. 57 +/- 10% at Pa,O2 31 mmHg). 5. These findings indicate that, in the rat, the hypocapnia that accompanies the hyperventilatory response to systemic hypoxia facilitates the tachycardia and may accentuate the renal vasodilation, but attenuate the hypoxia-induced vasodilatation in skeletal muscle. Possible mechanisms are discussed.

Pulmonary vascular effects of fat emulsion infusion in unanesthetized sheep. Prevention by indomethacin.

Pulmonary diffusing capacity and arterial blood Po(2) decrease in humans when 10% fat emulsion is infused. To study its effects on the pulmonary circulation and lung fluid balance, we infused 0.25 g/kg x h of a 10% fat emulsion (Intralipid, Cutter Laboratories, Inc., Berkeley, Calif.) into an awake sheep lung lymph preparation. The emulsion caused a sustained increase in pulmonary artery pressure to approximately twice base line with little change in left atrial pressure. Pa(O2) decreased an average 13 torr and lung lymph flow increased two- to threefold. Lymph/plasma total protein concentration fell as lymph flow increased; the magnitude of the lymph/plasma protein decrease was similar to that reported previously when lung vascular pressures were mechanically elevated. Heparin infusion (loading dose = 4,000 U, maintenance dose = 2,000 U/h) cleared the serum of triglycerides but did not alter the response to fat emulsion. Indomethacin infusion (loading dose = 5 mg/kg, maintenance dose = 3 mg/kg x h) blocked the rise in pulmonary artery pressure, the increase in lung lymph flow, and the fall in Pa(O2). Neither extravascular lung water nor [(14)C]urea lung vascular permeability surface area products were altered by fat emulsion infusion. We conclude that fat emulsion infusion in sheep increases lung microvascular filtration by increasing vascular pressures, but has no effect on vascular permeability. Since the effects are blocked by indomethacin, they may be prostaglandin mediated.

Carbon dioxide and venous return and their interaction as stimuli to ventilation in the cat.

1. Respiratory responses were measured in forty-seven cats, made decerebrate or anaesthetized with pentobarbitone or chloralose-urethane, to changes in the level of CO(2) infused into the inferior vena cava via an external oxygenator circuit or to changes in the volume of venous return or to the inhalation of CO(2).2. No consistent difference was found between the respiratory response to the increase in the level of CO(2) infused or CO(2) inhaled provided that the volume of venous return during both sets of tests was held constant at normal levels.3. If the volume of venous return was increased and the level of CO(2) infused maintained at levels such that V(CO2) did not increase, ventilation increased with a fall in P(a, CO2), a response lying approximately on the isometabolic curve.4. If the volume of venous return and the level of CO(2) infusion were raised together, a spectrum of intermediate respiratory responses was obtained which reproduced all those seen in earlier papers, in muscular exercise or other hypermetabolic states.5. None of the steady-state respiratory responses was significantly affected by bilateral vagotomy or section of the sinus nerves, though sinus nerve section slowed the responses to infused or inhaled CO(2) and they were then less precisely controlled.6. Additional experiments indicated that where CO(2) was infused or inhaled, the effective stimulus to respiration was an increase in mean P(a, CO2) in proportion to the CO(2) added and that the respiratory response to CO(2) was enhanced by reduced blood volume. How the changes in venous return were sensed and affected respiration, remains unclear.7. These results may explain why previous workers have obtained exaggerated respiratory responses to the infusion of CO(2) and why respiration increases rapidly at the start of exercise and is then maintained at high levels without discernible change in the chemical stimulus in arterial blood.

Arterial chemoreceptors, ventilation and heart rate in man.

1. Transient changes of heart rate (HR) and ventilation were recorded following step changes in alveolar gas composition in three healthy subjects. From a steady state of normo- or slightly hypercapnic hypoxia (PA,CO2 38-46 torr, PA,O2 50-60 torr) arterial chemoreceptor stimulation was transiently relieved by breathing a CO2-free mixture for two breaths, either pur O2 (causing a fall in PA,CO2 and a rise in PA,O2; O2 test) or a low O2 mixture (causing a fall in PA,CO2 without any change in PA, O2; CO2 test). For both test types ventilation was either allowed to change freely ('free-breathing' tests) or was consciously maintained at the pre-test level by the subjects ('controlled-breathing tests). The circulatory delay from the lungs to the ear was measured with a sensitive ear oximeter. 2. In all 'free-breathing' tests ventilation decreased significantly after a mean latency of 5.2 sec; the average lung-ear circulation time was 4.9 sec. HR increased slightly above pre-test levels in eighty-one of one hundred and four tests of all types, the changes being significant after a latency identical to that of the ventilatory changes. Except in the 'controlled-breathing' CO2 tests this early tachycardia was followed by a decrease in HR within the following 5-6 sec. 3. These findings indicate that the primary effect of withdrawal of arterial chemoreceptor stimulation in conscious man as in the anesthetized animal is tachycardia. The secondary development of bradycardia in 'free-breathing' CO2 tests is probably due to the operation of a lung reflex sensing changes in ventilation. The absence of bradycardia in 'controlled-breathing' CO2 tests and its presence in 'controlled-breathing' O2 tests, finally, suggest that relief of systemic hypoxia causes a slowing of the heart not due to lung reflexes but to some other mechanism which operates with a latency nearly twice as long as the arterial chemoreflex.

Acid-base and respiratory changes after prolonged exposure to 1% carbon dioxide.

1. The acid-base and respiratory status of fifteen healthy male subjects living in an atmosphere of 1% CO2 in air was studied over the course of 44 days, during an operational patrol in a nuclear submarine. 2. Observations were made during a control period before exposure to CO2, at 4 day intervals during the patrol, and finally during the period after its completion. Samples of arterial blood from each subject were analysed for Pa,co2, pH and Po2 immediately after collection. Concurrently mixed expired Pco1 and Po2, together with minute volume and respiratory rate, were measured. 3. A mild uncompensated respiratory acidosis in which arterial pH was depressed by 0·02 pH unit was demonstrated throughout the period of exposure to CO2. This was associated with an acute rise in Pa,co2 of 0·14 kPa, accompanied by an increase in minute volume from 11·5 to 15 l/min. By mid-patrol minute ventilation had returned to control value and a further elevation in Pa,co2 of 0·31 kPa was detected together with a rise in plasma bicarbonate of almost 1 mmol/l. 4. On return to air after completion of the patrol, the acid-base changes appeared to be quickly reversed. Minute volume decreased slightly initially, but it too subsequently returned to the control value. A fall in Pa,o2 of about 2·5 kPa was recorded at this time, together with a reduction in forced vital capacity of 8%.

Circulatory and respiratory changes during unilateral and bilateral cranial nerve IX and X block in two asthmatics.

1. The respiratory and circulatory effects of bilateral block of the IXth and Xth cranial nerves (IX and X) with local anaesthetic were studied in two subjects with obstructive airways disease (asthma). 2. In one subject bilateral block of IX and X decreased alveolar ventilation as evidenced by a rise in Pa,co2 and a fall in Pa,o2. There was no apparent ventilatory change in the other subject. The lung volumes (ERV and FRC) were unaffected by the block; however, the forced vital capacity and 1 s forced expired volume were slightly improved in both subjects. 3. During bilateral IX and X block neither subject showed a ventilatory response after 3 min of breathing 8·7% O2 in 91·3% N2. In one subject during a left-sided IX and X block, there was a normal hypoxic-ventilatory increase, whereas during a right-sided IX and X block the hypoxic-ventilatory response was slightly less than normal. 4. Unilateral IX and X block in both subjects produced tachycardia and hypertension which was approximately one half the increased heart rate and blood pressure that followed bilateral IX and X blockade. 5. Unlike the control responses, breathing 8·7% O2 in 91·3% N2 during bilateral IX and X block produced no change in heart rate and there was a continuous fall in the systemic blood pressure. The pulmonary arterial pressure, however, increased in response to hypoxia in the same manner as before the block.