Electromagnetic Flow Transducer Research Articles

Hemodynamic effects of endothelin-1 on ovine fetal pulmonary circulation

To determine the hemodynamic effects of endothelin-1 (ET-1) in the fetal pulmonary circulation, we studied pulmonary vascular responses to brief and prolonged intrapulmonary infusions of the peptide in nine chronically prepared late-gestation fetal sheep. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer, and a catheter placed in the LPA allowed ET-1 infusion directly into the left lung. Brief (10-min) infusions of ET-1 (12.5-100 ng/min) increased flow up to 212% of baseline without changing pulmonary artery pressure. With prolonged (120-min) infusion of ET-1 (50 ng/min), flow increased from 69 +/- 8 to 164 +/- 23 ml/min at 10 min (P less than 0.05) but then declined and was not different from baseline at 120 min. The gradient between mean pulmonary artery and aortic pressures did not change, suggesting no constriction of the ductus arteriosus. Systemic (vena caval) infusion of ET-1 (100 ng/min for 30 min) caused systemic and pulmonary hypertension, as mean pulmonary artery pressure increased from 43 +/- 1 to 51 +/- 2 mmHg (P less than 0.05) and remained elevated for 30 min after cessation of the ET-1 infusion. We conclude that intrapulmonary ET-1 is a potent fetal pulmonary vasodilator, but its dilator effect is transient during prolonged infusion. In contrast, systemic infusion causes sustained hypertension, suggesting differential effects of ET-1 on the pulmonary and systemic circulations. These findings demonstrate marked vasoactivity of ET-1 in the fetus, suggesting a potential role in the normal or abnormal transitional circulation.

Isoflurane Impairs the Function of Ischemic Myocardium in Acutely but Not in Chronically Instrumented Dogs

To compare the effects of isoflurane on ischemic myocardium in acutely and chronically instrumented animals, 12 mongrel dogs were monitored with electromagnetic or Doppler ultrasonic flow transducers and hydraulic occluders around the left circumflex coronary artery, pressure transducers in the left ventricle, and heparin-filled catheters in the descending aorta. Regional function of normal and ischemic myocardium was assessed by sonomicrometry. The hemodynamic effects of isoflurane (2% inspired concentration) were more pronounced in the acutely than in the chronically instrumented dogs. Decreases in mean arterial pressure (-47% +/- 5% in the acute and -22% +/- 4% in the chronic preparation, P less than 0.01), left ventricular contractility (-51% +/- 6% and -33% +/- 4%, P less than 0.01), and coronary perfusion pressure (-59% +/- 6% and -12% +/- 9%, P less than 0.01) were more distinct in the acutely instrumented animals. Although the reduction of regional function during isoflurane anesthesia was similar in normal myocardium in both preparations (-33% +/- 4% acute and -34% +/- 6% chronic preparation, not a significant difference), an exaggerated dysfunction was observed in the ischemic myocardium of the acutely instrumented dogs (-66% +/- 2% and -30% +/- 4%, P less than 0.01). It is concluded that acutely instrumented dogs respond to the hemodynamic effects of isoflurane, resulting in ischemic myocardial dysfunction, significantly more than do chronically instrumented dogs.

In Utero Ventilation Augments the Left Ventricular Response to Isoproterenol and Volume Loading in Fetal Sheep

In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial "immaturity," and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) during in utero oxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep greater than or equal to 2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 +/- 27 mL.kg-1.min-1). Individually, oxygen ventilation (136 +/- 11 mL.kg-1.min-1, p less than 0.001) and isoproterenol (48 +/- 11 mL.kg-1.min-1, p less than 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 +/- 98 mL.kg-1.min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 +/- 0.54 kPa to 0.82 +/- 0.39 kPa, p less than or equal to 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular afterload and right ventricular constraint.

Doppler echocardiographic assessment of fetal descending aortic and umbilical blood flows. Validation studies in fetal lambs.

Doppler ultrasound has been used to assess abdominal aortic and umbilical blood flows in the human fetus, but the accuracy of this approach has not been demonstrated in an animal model. We compared abdominal aortic and umbilical blood flows determined by Doppler echocardiography in 12 fetal lambs with invasive flow measurements using radionuclide-labeled microspheres and electromagnetic flow transducers. We varied fetal blood flow from 100 to 950 ml/min in the abdominal aorta and from 130 to 610 ml/min in the umbilical vein. Invasive and Doppler echocardiographic flow measurements correlated well at both sites (y = 68 + 1.02x, r = 0.94, and y = 33 + 1.1x, r = 0.91, respectively). A slight overestimation of flow using the Doppler method may require a correction factor to assess actual flow. The degree of overestimation was not systematically related to measurements taken in smaller vessels or at larger angles of incidence. The present study demonstrates that determination of abdominal aortic and umbilical venous flows by echocardiography and pulsed Doppler ultrasound is feasible. Doppler measurements appear to be suited to serial comparison of actual flow.

Fetal pulmonary vasodilation after exogenous platelet-activating factor

To determine the fetal pulmonary vascular response to platelet-activating factor (PAF), we studied the hemodynamic effects of the infusion of PAF directly into the left pulmonary artery in 21 chronically catheterized fetal lambs. Left pulmonary arterial blood flow (Q) was measured with electromagnetic flow transducers. Ten-minute infusions of low-dose PAF (10-100 ng/min) produced increases in Q from a baseline of 71 +/- 5 to 207 +/- 20 ml/min (P less than 0.001) without changes in pulmonary arterial pressure. Pulmonary vasodilation with PAF was further confirmed through increases in Q with brief (15-s) infusions and increases in the slope of the pressure-flow relationship as assessed by rapid incremental compressions of the ductus arteriosus during PAF infusion. Infusion of Lyso-PAF had no effect on Q or pulmonary arterial pressure. Treatment with CV-3988, a selective PAF receptor antagonist, but not with meclofenamate, atropine, or diphenhydramine and cimetidine blocked the response to PAF infusion and did not affect baseline tone. Systemic infusion of high-dose PAF (300 ng/min) through the fetal inferior vena cava increased pulmonary arterial pressure (46.5 +/- 1.0 to 54.8 +/- 1.9 mmHg, P less than 0.01) and aorta pressure (44.3 +/- 1.0 to 52.7 +/- 2.2 mmHg, P less than 0.01) while also increasing Q. Neither PAF nor CV-3988 changed the gradient between pulmonary arterial and aorta pressures, suggesting that PAF does not affect ductal tone. We conclude that PAF is a potent fetal pulmonary vasodilator and that the effects are not mediated through cyclooxygenase products or by cholinergic or histaminergic effects.

The in utero left ventricle of the fetal sheep: the effects of isoprenaline.

1. Isoprenaline was infused into in utero fetal lambs to examine the effect of this beta-adrenoceptor agonist on left ventricular stroke volume and left ventricular output and test the generally held assumption that the fetal ventricle is markedly limited in its ability to increase ventricular output. 2. Seven in utero lambs (121-133 days of gestation) were instrumented with left ventricular dimension transducers, an ascending aortic electromagnetic flow transducer, a brachiocephalic arterial catheter and electrocardiographic and atrial pacing electrodes. 3. On the day of study, 5-8 days following surgery and 129-137 days of gestation, each lamb received infusions of isoprenaline, via the superior vena cava or left atrium, at rates which ranged from 0.005-0.5 microgram kg-1 min-1. 4. Heart rate and left ventricular stroke volume, output and end-diastolic and end-systolic dimensions were measured under control conditions and during various levels of isoprenaline infusion, with and without controlling heart rate. 5. Analysis of variance was done using the mean cell model. Least-square means and standard errors of the least-square means are reported. F ratios were calculated from type III sums-of-squares; P less than 0.05 was considered significant. 6. The mean heart rate increased with isoprenaline (P less than 0.0001) from a mean control level of 169 +/- 8 to 281 +/- 9 beats min-1 (+/- S.E.M.). 7. Mean left ventricular end-diastolic and end-systolic minor axis dimensions decreased significantly with isoprenaline from 16.7 +/- 0.1 mm (control) to 15.7 +/- 0.2 mm (P less than 0.0004) and from 11.7 +/- 0.1 mm (control) to 10.4 +/- 0.2 mm (P less than 0.0001) respectively. When heart rate was controlled with atrial pacing, mean end-diastolic dimension increased significantly at the higher isoprenaline doses from 14.6 +/- 0.1 mm (control) to 15.3 +/- 0.2 mm (control) (P = 0.0002), while mean end-systolic dimension fell significantly from 10.9 +/- 0.1 to 10.5 +/- 0.1 mm (P less than 0.003). Inasmuch as stroke volume increased, the increase in end-diastolic dimension and the fall in end-systolic dimension indicate an increase in venous return to the left ventricle. 8. During spontaneous rhythm, isoprenaline increased stroke volume from 2.45 +/- 0.06 ml (control) to 2.63 +/- 0.09 ml, not statistically significant. When heart rate was controlled, stroke volume increased with isoprenaline dose from 1.68 +/- 0.06 ml (control) to 2.40 +/- 0.08 ml (P less than 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of increasing mean arterial pressure on left ventricular output in newborn lambs.

We developed a preparation in which the mean arterial pressure of the newborn lamb is varied with little change in left ventricular preload. Seven lambs underwent balloon atrial septostomy and were instrumented with vascular catheters, an electromagnetic flow transducer on the aorta, and a balloon occluder on the aorta. Four different preload conditions were established by volume infusion or withdrawal. Aortic flow was measured continuously during gradual occlusion of the aorta. Curves relating mean left atrial pressure to stroke volume before balloon inflation showed a plateau, with little increase in stroke volume with increases in atrial pressure above 7 mm Hg. With balloon inflation, stroke volume decreased linearly with increases in mean arterial pressure. Curves relating left atrial pressure to stroke volume constructed at constant mean atrial pressure showed no plateau but showed continued increases in stroke volume as left atrial pressure was increased to 10 mmHg. When mean arterial pressure is constant, the Starling mechanism is operative in newborn left ventricles. The plateau in newborn lamb function curves is due to increases in mean arterial pressure that accompany volume infusion.

Complete heart block in fetal lambs, I. Technique and acute physiological response

Prenatally diagnosed complete heart block (CHB), without associated cardiac anomalies, is often refractory to attempts to increase heart rate and cardiac output by medical therapy, and results in fetal death. We developed a model of CHB in fetal lambs in order to evaluate the acute physiological consequences of CHB and to assess the feasibility of fetal cardiac ventricular (V) and atrioventricular (AV) pacing. After hysterotomy and fetal sternotomy AV-sequential pacing leads were placed on the right atrium and ventricle (RV). Electromagnetic flow transducers were placed around the pulmonary artery and the ascending aorta to measure combined ventricular output (CVO) in normal sinus rhythm (NSR), CHB, AV, and V pacing. CHB block was successfully induced in 19 of 21 (90%) fetal lambs at 100 to 110 days' gestation by injection of formalin into the interventricular septum. Two fetuses were refractory to CHB despite multiple injections. The mean ventricular escape rate was 52 ± 3 (± SEM) beats/min (range, 45 to 60 beats/min). CHB lasted for the period of study (1 to 8 hours), and spontaneously reverted to NSR in one fetus after 3 hours. Combined ventricular output in NSR was 470 ± 31 mL/min (± SEM), which fell to 213 ± 13 mL/min in CHB, 45% of normal CVO ( P < .0001). CVO during AV-sequential and V pacing was 77% ( P = .02) and 62% ( P < .001), respectively, of combined ventricular output in NSR. Both RV (27%) and left ventricles (LV) (37%) showed compensatory increase in stroke volume during CHB. The RV was more adversely affected by loss of atrial kick with a 50% reduction in RV stroke volume versus 29% reduction in the LV stroke volume during V pacing compared with NSR. Transeptal formalin injection is a simple, reliable technique for inducing CHB in fetal lambs, with a success rate of 90%. The fetal heart demonstrates some compensatory increase in stroke volume in response to CHB. Ventricular and AV-sequential pacing are fessible in fetal lambs. RV stroke volume is more dependent on atrial kick than the LV. This model will allow the study of the pathophysiological response to CHB and the development of new clinical therapies for refractory cases in human fetuses.

Fentanyl Inhibits the Canine Carotid Chemoreceptor Reflex

To investigate the impact of fentanyl on the carotid chemoreceptor reflex, nine mongrel dogs were permanently monitored with electromagnetic flow transducers around the right common iliac artery and with heparin-filled catheters in the descending aorta and in one of the main carotid arteries with the tip just proximal to the carotid sinus. Carotid chemoreceptor activation (CCRA) produced by consecutive injections of nicotine (0.2-0.4 micrograms/kg) through the carotid catheter elicited bradycardia, expressed as an increase in cardiac cycle length by 140% +/- 18%, and a 252% +/- 16% increase in mean iliac arterial vascular resistance. These responses were markedly attenuated by fentanyl in a dose-dependent fashion: cardiac cycle length increased only by 50% +/- 7% (P less than 0.01) with 4 micrograms/kg and by 19% +/- 6% (P less than 0.01) with 8 micrograms/kg of intravenous fentanyl. These changes were paralleled by significantly (P less than 0.01) lesser increases in mean iliac arterial resistance (122% +/- 9% and 50% +/- 5%). It is concluded that fentanyl impairs the integrity of the carotid chemoreceptor reflex.

Effects of alveolar hypoxia on pulmonary capillary beds.

Using open chested dogs (n = 12), we tested the hypothesis that the pulmonary capillary changes its caliber in response to alveolar hypoxia. Animals were placed in a left upright lateral position. Pulmonary perfusion was measured by electromagnetic flow transducers attached to the main and left pulmonary arteries. Systemic artery, pulmonary artery and pulmonary vein pressures were measured via catheters inserted into them. Shunt flow through the pulmonary capillary beds was evaluated by the microsphere method, injecting a mixture of three different size (3, 9 and 15 microm) radioactive microspheres into the inferior vena cava. Right one lung ventilation with left lung atelectasis or left lung insufflation of 5 cmH2O (O2 or He) was achieved by occluding the left main bronchus with a blocker attached to an endotracheal tube. Right one lung ventilation caused redistribution of the perfusion from the left lung to the right lung. Left pulmonary vascular resistance increased significantly, while total pulmonary vascular resistance showed no significant changes. The shunt ratios of the 3 and 9 microm microspheres were not changed by right one lung ventilations with left lung atelectasis or insufflation. The shunt ratio of the 3 microm microspheres through the left lung was significantly higher than that through two lungs during both the two lung and one lung ventilations. We concluded that caliber changes in the pulmonary capillary do not occur in response to alveolar hypoxia.

Effects of increasing afterload on left ventricular output in fetal lambs.

Fetal ventricular performance has been considered limited because ventricular output does not increase with rapid volume expansion above mean left atrial pressures (mLAPs) of 5-7 mm Hg. To explore relations between preload, afterload, and stroke volume (SV) in the fetal left ventricle, we instrumented 126-129 days gestation fetal lambs with ascending aortic electromagnetic flow transducers, vascular catheters, and inflatable occluders around the aortic isthmus (n = 8) or descending aorta (n = 7). At 24-48 hours after surgery, blood was withdrawn or infused to reach various mLAPs. The aorta was then slowly occluded as aortic flow and mean arterial pressure (MAP) were measured continuously. Isthmus constriction produced linear decreases in SV as MAP increased; mLAP was unchanged. Descending aortic constriction produced no decrease in SV until high MAPs were reached. SV decreased as MAP increased further, and mLAP rose significantly. The curve relating mLAP and SV before constriction showed little increase in SV above mLAPs of 5-7 mm Hg; however, when curves were derived relating SV and mLAP at relatively constant MAPs, SV continued to increase even above an mLAP of 8-10 mm Hg. Our studies indicate that the fetal left ventricle responds to progressive increases in mLAP to at least 10 mm Hg. The lack of increase in SV above an mLAP of 5-7 mm Hg with rapid volume expansion is related to the concomitant increase in MAP and afterload.

Acute effects of angiotensin II on renal haemodynamics and excretion in conscious dogs.

The effects of a 60-min intravenous infusion of angiotensin II (A II; 4 or 20 ng A II/min/kg body weight) on renal blood flow (RBF; electromagnetic flow transducer, control value 19-25 ml/min/kg), glomerular filtration rate (GFR; control value 4.2-5.0 ml/min/kg), mean arterial blood pressure, sodium excretion, water excretion, and plasma A II and plasma aldosterone concentrations were examined in 6 chronically instrumented female conscious beagle dogs kept on three different dietary sodium intakes (SI): SI 0.5 or SI 2.5 mmol Na/kg/day or SI 4.5 mmol Na/kg/day plus an oral saline load prior to the experiment SI 4.5(+) dogs. Four nanograms A II decreased RBF and GFR in SI 4.5(+) dogs without changing the filtration fraction (FF%); in SI 0.5 dogs the RBF decreased, and the FF% increased. Twenty nanograms A II decreased RBF and increased FF% in all dietary protocols, less in SI 4.5(+) dogs. The mean arterial blood pressure increased in all dietary protocols by 10-15 mm Hg (4 ng A II) and 32-37 mm Hg (20 ng A II). Sodium and water excretions decreased by 32 and 46%, respectively, in SI 4.5(+) dogs at both doses of A II. The plasma aldosterone concentration increased in all but one protocol: 4 ng A II, SI 4.5(+) dogs. It is concluded that when A II plasma concentrations are most likely borderline to pathophysiological conditions (up to an average of 370 pg/ml), the GFR is less decreased than the RBF. This phenomenon also can be observed at lower plasma A II concentrations (average 200 pg/ml), when the renin-angiotensin system had been previously moderately activated.

Experimental ductus arteriosus: The relationships of atrial pressure, dilatation and flow with ANF secretion

The design of the study was to determine whether an increased blood flow as seen in shunt lesions could serve as a stimulus for the secretion of atrial natriuretic factor (ANF). Since atrial pressure, flow, and dilatation are closely related, an experimental ductus arteriosus model was utilized, in which acute changes of flow are assumed not to dilate the left atrium. In six dogs, a Dacron graft was constructed between the main pulmonary artery and the innominate artery. Constricting and releasing the tape around the graft adjusted the amount of “ductal” shunting. The total pulmonary flow and the shunt flow were measured by electromagnetic-flow transducers around the aortic root and around the graft. Plasma ANF concentration was measured from both cardiac atria. The size of the left atrium was determined from echocardiographic measurements made from a short-axis view. The total pulmonary flow varied between 1.2 and 5.8 1/min. The highest measured ANF was 396 pg/ml, and this was from the left atrium when the pressure was 18 mmHg, the highest left atrial pressure recorded. The highest right atrial pressure (5 mmHg) also correlated with the highest right atrial level of ANF (366 pg/ml). The right atrial pressure had a significant correlation with plasma ANF concentration (R = 0.43, p < 0.05). Pulmonary flow and plasma ANF concentration did not correlate; neither did left atrial size and ANF levels in 16 flow states where the size was measured. In the absence of atrial dilatation there was minimal stimulus for ANF secretion. A transient increase of left atrial pressure, without a concomitant significant atrial dilatation, did not serve as a significant stimulus for ANF secretion.

Efficiency of Work of Inspiratory Muscles in Standing and in Exercising Dogs

The objective of this study was to elucidate the resistive, elastic, and total inspiratory muscle work and mainly the efficiency of the inspiratory muscle work in still standing and in exercising dogs. In 180 experiments with nine mongrel dogs, respiratory and circulatory functions were recorded at rest and during a 1.5-mph walk on a treadmill belt which was inclined by 9 degrees. Each dog had been trained and surgically prepared before the series of experiments started. An electronic pressure transducer together with a fluid-filled catheter was attached to the ribs at the midthoracic level. Airflow was monitored with a pneumotachygraph attached to a face mask. Aortic flow was monitored with an electromagnetic flow transducer. Catheters in the atria, the ventricles, and the pulmonary and systemic vessels were used to determine hemodynamic parameters and blood gas levels. All recorded and all derived functions were evaluated by a dedicated computer. At rest, resistive inspiratory work (0.98 kg cm) was smaller than elastic work (1.36 kg cm). Elastic work did not change with exercise but resistive work increased to 1.46 kg.cm. The increase of total work from 2.33 kg.cm at rest to 2.79 kg.cm during exercise did not reach significance. Inspiratory power increased with exercise. Estimated diaphragmatic oxygen consumption increased from 2.23 ml/min at rest to 3.64 ml/min during exercise. It was 1.6 percent of the total oxygen consumption at rest and 1.7 percent of the total oxygen consumption during exercise. The estimated efficiency of the work of inspiratory muscles was 15.8 percent at rest and 25.8 percent during exercise. These values did not vary substantially between different animals.

Conceptus development, uterine response, blood gases and endocrine function of gilts exposed to increased ambient temperature during early pregnancy

Fifteen crossbred gilts were used to determine the influence of heat stress during Days 8 to 16 after onset of estrus on the development of conceptuses and uterine and endocrine functions. Ten gilts were bred 12 and 24 h after the onset of estrus (Day 0), and five gilts were nonbred controls. On Day 5, catheters were inserted into the uterine-ovarian vein (UV), saphenous artery (SA) and saphenous vein (SV) of each gilt. An electromagnetic blood flow transducer was implanted around the main uterine artery. Pregnant (n=5) and nonbred (n=5) control gilts were exposed to 21 ± 1°C, and pregnant heat-stressed gilts (n=5) were exposed to 37 ± 1°C for 12 h and 32 ± 1°C for 12 h daily during Days 8 through 16 after estrus. Treatment did not influence the partial pressure of oxygen (PO 2) and of carbon dioxide (PCO 2) in the UV, SA and SV blood. Uterine blood flow was not altered by heat stress. On Day 16, total wet weight of conceptuses was reduced in the gilts that were heat-stressed compared with conceptuses from control gilts. Incorporation of 3H-leucine into macromolecules in vitro by conceptuses from the heat-stressed gilts was reduced compared with control gilts. Concentrations of 15-keto-13, 14-dihydro prostaglandin F 2α (PGFM) in peripheral blood were greater than 1 ng/ml between Days 13 to 16 after estrus in 20% of the pregnant control gilts, 60% of the heat-stressed pregnant gilts, and 100% of the nonbred gilts. Concentrations of estradiol in the SA were affected by treatment. These results indicate that heat stress of gilts between Days 8 to 16 after estrus reduced the amount of conceptus tissue and altered concentrations of estradiol in the peripheral circulation, but uterine blood flow and PO 2 and PCO 2 in blood were not affected.

Myocardial reactive hyperemia in the newborn

Adenosine may be an important metabolic regulator of coronary blood flow during active hyperemia in the newborn. In this study, the adenosine uptake blocker dipyridamole (DPY) and receptor antagonist theophylline (THEO) were used to assess the role of adenosine in the reactive hyperemic response of the neonatal heart. Eighteen anesthetized, open-chest lambs were instrumented with aortic and coronary sinus catheters as well as an extracorporeal shunt to the circumflex coronary artery incorporating a 2.0-mm electromagnetic flow transducer. Ten-second occlusions of the circumflex coronary artery catheter were performed, and the resulting reactive hyperemia was used to determine peak hyperemic blood flow (PHF), duration of hyperemia, and the blood flow repayment. These values were determined prior to treatment and 30 min following administration of a saline vehicle, DPY (0.2 mg/kg) or THEO (5 mg/kg). DPY resulted in increases in PHF from 220 ± 12 to 247 ± 14 ml/min/100 g heart tissue ( P < 0.05), durations of hyperemia from 29 ± 2 to 38 ± 2 sec ( P < 0.01), and blood flow repayments from 65 ± 2 to 102 ± 4 ml/100 g ( P < 0.001). THEO resulted in decreases in PHF from 224 ± 15 to 198 ± 12 ml/min/100 g ( P < 0.05), durations of hyperemia from 28 ± 2 to 22 ± 2 sec ( P < 0.05), and blood flow repayments from 64 ± 2 to 46 ± 2 ml/100 g ( P < 0.01). The data indicate that DPY enhances reactive hyperemia while antagonism of adenosine with THEO attenuates it. These results suggest that adenosine plays a role in mediating reactive hyperemia in the newborn heart.

Effect of beta-adrenergic receptor blockade on responses to acute hypoxemia in lambs.

We studied the effects of beta-adrenergic receptor blockade on general circulatory and metabolic responses to moderate (FIO2 = 0.09) acute hypoxemia in newborn (protocol 1) and 3-wk-old (protocol 2) lambs, and on regional blood flow distribution in newborn lambs (protocol 1). Via a left thoracotomy we placed an electromagnetic flow transducer around the ascending aorta and inserted various vascular catheters. After 2 days of recovery, the lambs were studied. In protocol 1, we measured cardiovascular variables and regional blood flow distribution during control conditions, after 45 min of acute hypoxemia, and after 0.5 mg/kg of propranolol during acute hypoxemia. In protocol 2, we measured cardiovascular variables during control conditions and after 45 min of acute hypoxemia with and without propranolol pretreatment. In both groups, propranolol limited the increase in cardiac output and heart rate caused by hypoxemia, and thus decreased oxygen delivery. However, propranolol also decreased oxygen consumption so that pulmonary arterial pO2 was either higher (protocol 1) or the same (protocol 2) as during acute hypoxemia alone. Neither metabolic acidosis nor hypothermia ensued. In protocol 1, propranolol decreased renal, carcass, and most importantly, myocardial blood flows. However, myocardial O2 consumption also fell, coronary sinus pO2 increased, and blood was redistributed toward the subendocardium, suggesting that myocardial perfusion improved. Thus, beta-adrenergic receptor blockade during acute moderate hypoxemia may have a beneficial effect by reducing total body and myocardial oxygen demand in excess of the reduction in oxygen delivery.

Temporal response of the fetal pulmonary circulation to pharmacologic vasodilators.

To determine the temporal response of the fetal pulmonary circulation to pharmacologic vasodilators and to assess vasoreactivity following vasodilation, we infused either acetylcholine, histamine, or bradykinin directly into the left pulmonary artery of 21 chronically prepared fetal sheep. Blood flow (Q) to the left lung was measured by electromagnetic flow transducer. Left pulmonary artery infusion of acetylcholine at 1.5 micrograms.min-1 for 2 hr produced an increase in Q from 59 +/- 8 ml.min-1 to a peak of 113 +/- 10 ml.min-1 at 20 min into the infusion (P less than 0.001). After the peak at 20 min, Q steadily declined toward baseline to 66 +/- 7 ml.min-1 at the end of the 2-hr infusion period (P less than 0.01). Q in the 1/2-hr period following infusion was significantly less than the baseline period (47 +/- 6; P less than 0.04) with no change in pulmonary artery pressure. Similar patterns were seen with 2-hr infusions of histamine (150 ng.min-1) and bradykinin (100 ng.min-1). After a 2-hr infusion of one of the agents, a repeat infusion with that agent or a different one resulted in a diminished response. We conclude that fetal pulmonary vasodilation in response to local infusion of acetylcholine, histamine, or bradykinin is not sustained over a 2-hr period, and that following 2-hr exposure to vasodilators, pulmonary vascular resistance is increased and pulmonary vasoreactivity to pharmacologic vasodilators is decreased.

An increment in unilateral carotid blood flow produces cerebral aneurysms in rats.

To study the effect of haemodynamic stress on cerebral aneurysm development, three groups of adult Wistar rats were used: 1) One group with ligation of the right common carotid artery; 2) One with an end-to-side common carotid artery anastomosis and 3) Another group that was sham-operated. Blood flow through the left common carotid artery was measured with an electromagnetic flow transducer (0.85 mm in diameter) in anesthetized animals. Before the experimental intervention, the mean carotid blood flow was 2.8 +/- 0.14 ml/min. Following carotid ligation the blood flow in the patent carotid artery increased 25 +/- 5% after 7 +/- 0.3 days and 37 +/- 18% after 149 +/- 23 days; whereas following carotid anastomosis, carotid blood flow increased 102 +/- 16% after 9.6 +/- 2 days and 103 +/- 35% after 169 +/- 15 days. The sham operation did not significantly affect carotid blood flow. Control values for mean arterial pressure (102 +/- 3 mmHg) and blood gases (PaO2 = 106 +/- 3.4 mmHg, PaCO2 = 38 +/- 1.2 mmHg and pH = 7.32 +/- 0.02) were similar in the three groups of rats and did not change significantly over time after the experimental procedure. Necropsy was carried out 149 +/- 15 days after the experimental intervention. No cerebral aneurysms were found in the rats with carotid ligation or which had been sham-operated, however, three of the eight rats (p less than 0.05) with carotid anastomosis presented single aneurysms in the anterior cerebral-anterior communicating arterial complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent fetal pulmonary hypoperfusion after acute hypoxia

To determine the effects of duration of hypoxia on fetal pulmonary blood flow and vasoreactivity, we studied the response of the fetal pulmonary vascular bed before, during, and after prolonged (2-h) and more brief (30-min) exposures to acute hypoxia in 19 chronically instrumented unanesthetized fetal lambs. Left pulmonary arterial blood flow was measured by an electromagnetic flow transducer. Fetal PO2 was lowered by delivering 10-12% O2 to the ewe. During 2-h periods of hypoxia left pulmonary arterial blood flow decreased, and main pulmonary arterial and pulmonary vascular resistance increased. The increase in pulmonary vascular resistance was sustained throughout the 2-h period of hypoxia. After the return of the ewe to room air breathing, pulmonary vascular resistance remained elevated for at least 1 h despite the rapid correction of hypoxemia and in the absence of acidemia. In contrast, after 30 min of hypoxia, left pulmonary arterial blood flow, pulmonary arterial pressure, and pulmonary vascular resistance returned to base-line values rapidly with the termination of hypoxia. The persistent pulmonary hypoperfusion after 2 h of hypoxia was attenuated by alpha-adrenergic blockade and was characterized by a blunted vasodilatory response to increases in fetal PO2. When fetal PO2 was elevated during the posthypoxia period in the presence of alpha-blockade, pulmonary blood flow still remained unresponsive to increases in fetal PO2. We conclude that 2-h periods of acute hypoxia can decrease fetal pulmonary vasoreactivity, and we speculate that related mechanisms may contribute to the failure of the normal adaptation of the pulmonary circulation at birth.