Hemodynamic mechanisms of the pulmonary artery pressure and blood flow changes following vasoactive pressor drugs injection

The character and values of changes of the pulmonary and systemic hemodynamics following epinephrine, norepinephrine and angiotensin intravenous injection were studied in acute experiments on the anesthetized cats. After catecholamines injection pulmonary blood flow was always increased, meanwhile pulmonary artery pressure can be elevated (in the most observations) or decreased. In the cases of angiotensin administration the pulmonary blood flow could be augmented or decreased; pulmonary artery pressure had been increased or decreased independently from the character of changes of pulmonary flow. Thus, linear correlation between shifts of the pulmonary artery pressure and pulmonary blood flow had not been revealed. The changes of the pulmonary artery pressure were not correlated with the pulmonary vascular resistance ones; however they had strong relationship with the changes of the left atrial pressure. If the left atrial pressure was decreased the pulmonary artery pressure elevation was less, comparing with its values in experiments, where the left atrial pressure was increased; in the case of depressor shifts of pulmonary artery pressure, the left atrial pressure was also decreased. The character and values of the pulmonary blood flow changes were strongly correlated with the changes of the venous return; however they had no linear correlations with the right and left atrial pressures and pulmonary vascular resistance changes. Thus we concluded, that hemodynanics mechanisms of the pulmonary artery pressure and flow changes following vasoactive pressor drugs injection changes are different.     

Bedside determination of left atrial pressure

An investigation was conducted to assess the accuracy of left heart filling pressures determined by a right heart catheter introduced at the bedside. Twelve patients were studied after open cardiac surgery by simultaneously recording pressures from both sides of the pulmonary capillary bed with a direct left atrial catheter and a flow-directed pulmonary arterial catheter. The mean pulmonary artery “occluded” pressure was shown to be a highly reliable index of mean left atrial pressure in all cases. It was much more accurate than pulmonary end-diastolic pressure, especially in six patients with pre-existing pulmonary hypertension.     

Hemodynamic Response to Exercise After Beta-Adrenergic Blockade with Propranolol in Patients with Mitral Valve Obstruction

Propranolol (P) .13 mg./kg. was given to seven patients with mitral valve obstruction the changes in resting and exercise hemodynamics were followed by means of combined right and left heart catheterization. Changes were variable. At rest there was a decrease in heart rate of 10 beats/min. with no consistent change in stroke volume, cardiac output, left ventricular systolic (LVS) or left atrial (LA) pressure after P. Mean left ventricular end-diastolic (LVED) pressure was increased 3 mm., mean pulmonary artery (PA) pressure was increased 4 mm., and mean mitral valve gradient was reduced 3 mm. Hg by P. During exercise, mean LVS pressure was decreased 31 mm., mean LVED pressure increased 3 mm., mean LA pressure decreased 3 mm., and mean mitral valve gradient was reduced 5 mm. Hg after P. Mean exercise PA pressure was unchanged, cardiac output was reduced 0.9 1./min., and mean heart rate was reduced 37 beats/min., while stroke volume increased 3 ml./beat after P. Exercise pulmonary vascular resistance was increased from 6.1 to 8.2 units by P. Despite a slower heart rate, the diastolic filling period was not increased. P has no place in the treatment of the majority of patients with mitral stenosis because it further reduces cardiac performance below normal.     

The pulmonary hemodynamics changes under experimental myocardial ischemia in rabbits following increased arterial pressure

In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the infusion of adrenaline and phenylephrine. The pulmonary artery pressure was increased following infusion of these drugs; however, it decreased to normal level in the condition of myocardial ischemia. Meanwhile the pulmonary vascular resistance was elevated to the same level in both cases. Following adrenaline infusion, the pulmonary artery blood flow and venous return increased and, in the condition of myocardial ischemia, they decreased to normal level, but the left atrial pressure was decreased. Following phenylephrine infusion, the pulmonary artery blood flow and venous return did not change and, in the condition of myocardial ischemia, these parameters decreased lower than normal level but the left atrial pressure was elevated. Thus we concluded that equal values of the pulmonary artery pressure in both cases were caused by changes of different character in the left atrial pressure. The differences of the changes character and values of the pulmonary artery flow under experimental myocardial ischemia following the infusion of adrenaline and phenylephrine were caused by different shifts of the venous return.     

Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation.

We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure.     

Microvascular pressure profile in intact in situ lung.

We measured the microvascular pressure profile in lungs physiologically expanded in the pleural space at functional residual capacity. In 29 anesthetized rabbits a caudal intercostal space was cleared of its external and internal muscles. A small area of endothoracic fascia was surgically thinned, exposing the parietal pleura through which pulmonary vessels were clearly detectable under stereomicroscopic view. Pulmonary microvascular pressure was measured with glass micropipettes connected to a servo-null system. During the pressure measurements the animal was kept apneic and 50% humidified oxygen was delivered in the trachea. Pulmonary arterial and left atrial pressures were 22.3 +/- 1.5 and 1.6 +/- 1.5 (SD) cmH2O, respectively. The segmental pulmonary vascular pressure drop expressed as a percentage of the pulmonary arterial to left atrial pressure was approximately 33% from pulmonary artery to approximately 130-microns-diam arterioles, 4.5% from approximately 130- to approximately 60-microns-diam arterioles, approximately 46% from approximately 60-microns-diam arterioles to approximately 30-microns-diam venules, approximately 9.5% from 30- to 150-microns-diam venules, and approximately 7% for the remaining venous segment. Pulmonary capillary pressure was estimated at approximately 9 cmH2O.     

Bedside evaluation of the resistance of large and medium pulmonary veins in various lung diseases.

To evaluate the contribution of large and medium pulmonary veins to the total pulmonary vascular resistance in various human lung diseases, we compared in 64 patients the pulmonary arterial proximal wedge pressure (Ppw), obtained when the balloon of a 7F pulmonary artery catheter was inflated with 1.5 ml air, with the distal wedge pressure (Pdw), obtained after the tip of the catheter was advanced until wedged in a small artery without balloon inflation. Ppw, reflecting the pressure in a large pulmonary vein, approximates the left atrial pressure, whereas Pdw reflects the pressure in a smaller pulmonary vein. Pdw was greater than Ppw in all 64 patients. The Pdw-Ppw gradient was 1.1 +/- 0.5 mmHg in nine patients with normal lungs and was significantly higher in 13 patients with chronic congestive heart failure (3.8 +/- 0.8 mmHg, P less than 0.01) and in 22 patients with adult respiratory distress syndrome (3.8 +/- 0.8 mmHg; P less than 0.01), but not in 20 patients with chronic obstructive pulmonary disease (1.8 +/- 0.7 mmHg). The distribution of the pulmonary vascular resistance was clearly different among the four groups. The fraction of the total pulmonary vascular resistance attributable to large and medium pulmonary veins was significantly increased (P less than 0.01) in adult respiratory distress syndrome (27.5 +/- 12%) and cardiac patients (27.5 +/- 9%) compared with patients with chronic obstructive pulmonary disease (13 +/- 5%) and normal lungs (13.5 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Methylene blue selectively inhibits pulmonary vasodilator responses in cats

The effects of methylene blue on vascular tone and the responses to pressor and depressor substances were investigated in the constricted feline pulmonary vascular bed under conditions of controlled blood flow and constant left atrial pressure. When tone was elevated with U46619, intralobar injections of acetylcholine, bradykinin, nitroglycerin, isoproterenol, epinephrine, and 8-bromoguanosine-3',5'-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intralobar infusions of methylene blue elevated lobar arterial pressure without altering base-line left atrial or aortic pressure, heart rate, or cardiac output. When methylene blue was infused in concentrations that raised lobar arterial pressure to values similar to those attained during U46619 infusion, the pulmonary vasodilator responses to acetylcholine, bradykinin, and nitroglycerin were reduced significantly, whereas vasodilator responses to isoproterenol, epinephrine, and 8-bromo-cGMP were not altered. Moreover, the pressor responses to angiotensin II and BAY K 8644 during U46619 infusion and during methylene blue infusion were similar. The enhancing effects of methylene blue on vascular tone and inhibiting effects of this agent on responses to acetylcholine, bradykinin, and nitroglycerin were reversible. These responses returned to control value when tone was again increased with U46619, 30-45 min after the methylene blue infusion was terminated. The present data are consistent with the hypothesis that cGMP may play a role in the regulation of tone in the feline pulmonary vascular bed and in the mediation of vasodilator responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin, and to nitrogen oxide-containing vasodilators such as nitroglycerin.     

Relations between changes of the pulmonary and systemic hemodynamics following neurogenic stimuli

The character and values of changes of the pulmonary and systemic hemodynamics following neurogenic stimuli application on the cardiovascular system were studied in acute experiments on the anesthetized cats. Vagus nerve stimulation reduced the heart rate and decreased myocardial contractility in result, right and left atrial pressure increased, whereas pulmonary pressure and flow, venous return, cardiac output and venous return decreased. Pulmonary pressure reached maximal level and returned to the initial value earlier than the pulmonary flow. On the contrary, pulmonary pressure, following neurogenic pressor stimuli, reached maximal level and returned to the initial value later than the pulmonary flow; the sign of the changes of the pulmonary pressure could be positive or negative, whereas pulmonary flow were always increased. The venous return did not change, and for this reason it could not cause the increasing of pulmonary flow which was elevated following increasing of the heart rate and myocardial contractility. The shifts of the pulmonary pressure were correlated with the pulmonary resistance those, which were increased after the stellate ganglion stimulation and decreased following carotid reflex; they did not change in case of sciatic nerve stimulation. The shifts of the pulmonary pressure did not depended on the decreased right and left atrial pressures. When the pulmonary flow was always increased, the cardiac output following electrical stimulation of the stellate ganglion and sciatic nerve was elevated, and it was decreased following carotid reflex, i. e. linear correlation between these parameters were not found. Pulmonary and systemic arterial pressure changes were more obvious in case of direct neurogenic stimuli application comparing with reflectory ones; in both cases, the positive chrono- and inotropic cardiac effects were similar.     

Atrial septostomy benefits severe pulmonary hypertension patients by increase of left ventricular preload reserve

At present, it is unknown why patients suffering from severe pulmonary hypertension (PH) benefit from atrial septostomy (AS). Suggested mechanisms include enhanced filling of the left ventricle, reduction of right ventricular preload, increased oxygen availability in the peripheral tissue, or a combination. A multiscale computational model of the cardiovascular system was used to assess the effects of AS in PH. Our model simulates beat-to-beat dynamics of the four cardiac chambers with valves and the systemic and pulmonary circulations, including an atrial septal defect (ASD). Oxygen saturation was computed for each model compartment. The acute effect of AS on systemic flow and oxygen delivery in PH was assessed by a series of simulations with combinations of different ASD diameters, pulmonary flows, and degrees of PH. In addition, blood pressures at rest and during exercise were compared between circulations with PH before and after AS. If PH did not result in a right atrial pressure exceeding the left one, AS caused a left-to-right shunt flow that resulted in decreased oxygenation and a further increase of right ventricular pump load. Only in the case of severe PH a right-to-left shunt flow occurred during exercise, which improved left ventricular preload reserve and maintained blood pressure but did not improve oxygenation. AS only improves symptoms of right heart failure in patients with severe PH if net right-to-left shunt flow occurs during exercise. This flow enhances left ventricular filling, allows blood pressure maintenance, but does not increase oxygen availability in the peripheral tissue.     

Effects of pneumatic antishock garment inflation in normovolemic subjects

This study examines the effects of inflation of pneumatic antishock garments (PASG) in 10 normovolemic men (mean age 44 +/- 6 yr) undergoing diagnostic catheterization. Seven subjects had normal heart function and no evidence of coronary artery disease (CAD); three patients had CAD. High-fidelity multisensor catheters were employed to simultaneously record right and left heart pressures before PASG inflation and after inflation to 40, 70, and 100 mmHg. A thermal dilution catheter was used to obtain pulmonary capillary wedge pressure and cardiac output. Counterpressure increases greater than or equal to 40 mmHg were associated with significant changes in left and right heart pressures. Right and left ventricular end-diastolic pressures increased 100% (P less than 0.01); mean pulmonary arterial and aortic pressures increased 77 and 25%, respectively (P less than 0.01); systemic vascular resistance increased 22% (P less than 0.05) and pulmonary vascular resistance did not change in normal subjects at maximum PASG inflation. Heart rate, cardiac output, and aortic and pulmonary arterial pulse pressures did not change during inflation in either group. Right and left ventricular end-diastolic pressures and pulmonary capillary wedge pressure were greater (P less than 0.05) in the CAD group compared with the normal subjects during PASG inflation. The data suggest that the primary mechanism whereby PASG inflation induces changes in central hemodynamics in normovolemic subjects is through an acute increase in left ventricular afterload. PASG changes in afterload and pulmonary capillary wedge pressure imply that these devices should be used with caution in patients with compromised cardiac function.     

慢阻肺伴左心衰竭临床特征与影响因素分析

摘要 目的：探讨慢阻肺伴左心衰竭临床特征与影响因素。方法：回顾性选择2019年1月至2020年12月来我院诊治的慢性阻塞性肺疾病患者150例。根据是否合并心衰,将150例患者分为慢阻肺伴左心衰竭组（A组）与慢阻肺未伴左心衰竭组（B组）。分析150例患者中慢阻肺伴左心衰竭的占比,分析对比两组一般资料、习惯和疾病病史、肺功能、心脏彩超、心电图结果、血液指标水平与动脉血气指标,采用Logistic回归分析慢阻肺伴左心衰竭的影响因素。结果：（1）150例患者中,慢阻肺伴左心衰竭者占比为32.00 %,慢性阻塞性肺疾病未合并左心衰竭者占比为68.00 %。（2）两组性别、年龄、患病时间、糖尿病史、吸烟史、高血压史、冠心病史、FEV1/FVC、左房内径、左心室舒张末内径、左室重量分数、左室后壁厚度、肺动脉压、血小板计数、C反应蛋白、降钙素原、凝血酶原时间、D-二聚体、白蛋白、肌酸激酶同工酶、N末端脑钠肽前体、PaCO₂、PaO₂、SaO₂对比有差异（P<0.05）。（3）Logistic回归分析结果表明、性别、年龄、糖尿病史、吸烟史、高血压史、冠心病史、左心室舒张末内径、肺动脉压是影响慢阻肺合并左心衰竭患者的影响因素（P<0.05）。结论：慢阻肺伴左心衰竭的占比较高,其与性别为男性、年龄偏大、有糖尿病史、吸烟史、高血压史、冠心病史、左心室舒张末内径升高、肺动脉压升高相关,需对以上因素给予积极干预及治疗。     

Computational modeling of left heart diastolic function: examination of ventricular dysfunction

A computational model that accounts for blood-tissue interaction under physiological flow conditions was developed and applied to a thin-walled model of the left heart. This model consisted of the left ventricle, left atrium, and pulmonary vein flow. The input functions for the model included the pulmonary vein driving pressure and time-dependent relationship for changes in chamber tissue properties during the simulation. The Immersed Boundary Method was used for the interaction of the tissue and blood in response to fluid forces and changes in tissue pathophysiology, and the fluid mass and momentum conservation equations were solved using Patankar's Semi-Implicit Method for Pressure Linked Equations (SIMPLE). This model was used to examine the flow fields in the left heart under abnormal diastolic conditions of delayed ventricular relaxation, delayed ventricular relaxation with increased ventricular stiffness, and delayed ventricular relaxation with an increased atrial contraction. The results obtained from the left heart model were compared to clinically observed diastolic flow conditions, and to the results from simulations of normal diastolic function in this model [1]. Cases involving impairment of diastolic function were modeled with changes to the input functions for fiber relaxation/contraction of the chambers. The three cases of diastolic dysfunction investigated agreed with the changes in diastolic flow fields seen clinically. The effect of delayed relaxation was to decrease the early filling magnitude, and this decrease was larger when the stiffness of the ventricle was increased. Also, increasing the contraction of the atrium during atrial systole resulted in a higher late filling velocity and atrial pressure. The results show that dysfunction can be modeled by changing the relationships for fiber resting-length and/or stiffness. This provides confidence in future modeling of disease, especially changes to chamber properties to examine the effect of local dysfunction on global flow fields.     

Effect of increased left atrial pressure on breathing frequency in anesthetized dog

Distension or loading of the isolated canine left heart caused reflex tachypnea in prior studies. The object of the present effort was to explore the possibility that this depended primarily on atrial distension. Cardiopulmonary bypass perfusion and ligation of pulmonary veins were used to isolate the left-heart chambers of anesthetized dogs. Simultaneous distension of the beating left atrium and fibrillating ventricle stimulated breathing frequency (f), whereas isolated ventricular distension did not. At other times, intervals of atrial fibrillation were imposed under two different conditions: 1) while the right heart and lungs were bypassed and systemic perfusion was provided by the left ventricle using blood returned to the left atrium by pump and 2) while the ventricles fibrillated and systemic perfusion was supplied directly by the pump. Atrial fibrillation increased left atrial pressure and stimulated f in condition 1. In condition 2, f increased only if fibrillation was associated with a rise in left atrial pressure. Vagal cooling blocked the effect of fibrillation. I conclude that left atrial distension may initiate reflex tachypnea.     

Sudden,Severe Mitral Insufficiency

Five male patients with sudden, severe mitral insufficiency due solely to ruptured chordae tendineae or papillary muscle had an abrupt onset of symptoms of left and right heart failure and the sudden appearance of a harsh, widely propagated apical pansystolic murmur. None had a history of rheumatic fever. All were in sinus rhythm and had but mild left atrial and ventricular enlargement. Giant left atrial “v” waves were characteristic and exceeded pulmonary artery pressure in two instances.In contrast, when ruptured chordae tendineae were superimposed on chronic rheumatic mitral insufficiency, females predominated and there was a long history of disability. Atrial fibrillation, less elevation of left atrial pressure, and marked left atrial and ventricular enlargement were characteristic. These latter patients closely resembled patients with chronic rheumatic mitral insufficiency alone.It is concluded that the syndrome of sudden, severe mitral insufficiency develops if ruptured chordae tendineae occur on a previously normal or insignificantly diseased mitral valve. If ruptured chordae tendineae are superimposed on chronic rheumatic mitral insufficiency, the syndrome resembles that seen in the latter alone.     

Orthogonal P-wave morphology is affected by intra-atrial pressures

Background

It has previously been shown that the morphology of the P-wave neither depends on atrial size in healthy subjects with physiologically enlarged atria nor on the physiological anatomical variation in transverse orientation of the left atrium. The present study aimed to investigate if different pressures in the left and right atrium are associated with different P-wave morphologies.

Methods

38 patients with isolated, increased left atrial pressure, 51 patients with isolated, increased right atrial pressure and 76 patients with biatrially increased pressure were studied. All had undergone right heart catheterization and had 12-lead electrocardiographic recordings, which were transformed into vectorcardiograms for detailed P-wave morphology analysis.

Results

Normal P-wave morphology (type 1) was more common in patients with isolated increased pressure in the right atrium while abnormal P-wave morphology (type 2) was more common in the groups with increased left atrial pressure (P = 0.032). Moreover, patients with increased left atrial pressure, either isolated or in conjunction with increased right atrial pressure, had significantly more often a P-wave morphology with a positive deflection in the sagittal plane (P = 0.004).

Conclusion

Isolated elevated right atrial pressure was associated with normal P-wave morphology while left-sided atrial pressure elevation, either isolated or in combination with right atrial pressure elevation, was associated with abnormal P-wave morphology.

     

Pulmonary pressure-flow relationships in the fetal lamb during in utero ventilation

Pressure-flow relationships in the ventilated lung have not been previously determined in undelivered fetal sheep. Therefore we studied 11 late-gestation chronically prepared fetal sheep during positive-pressure ventilation with different gas mixtures to determine the roles of mechanical distension and blood gas tensions on pressure-flow relationships in the lung. Ventilation with 3% O2-7% CO2 produced a substantial fall in pulmonary vascular resistance even though arterial blood gases were not changed. Increases in pulmonary arterial PO2 during ventilation were associated with falls in pulmonary vascular resistance beyond that measured during mechanical distension. Decreases in pulmonary arterial PCO2 and associated increases in pH were also associated with falls in pulmonary vascular resistance. Pulmonary blood flow ceased at a pulmonary arterial pressure that exceeded left atrial pressure, indicating that left atrial pressure does not represent the true downstream component of driving pressure through the pulmonary vascular bed. The slope of the driving pressure-flow relationship in the normal mature fetal lamb was therefore different from the ratio of pulmonary arterial pressure to pulmonary arterial flow. We conclude that mechanical ventilation, increased PO2 and decreased PCO2, and/or increased pH has an important influence on the fall in pulmonary vascular resistance elicited by positive pressure in utero ventilation of the fetal lamb and that the downstream driving pressure for pulmonary blood flow exceeds left atrial pressure.     

Fluid–structure interaction in a fully coupled three-dimensional mitral–atrium–pulmonary model

This paper aims to investigate detailed mechanical interactions between the pulmonary haemodynamics and left heart function in pathophysiological situations (e.g. atrial fibrillation and acute mitral regurgitation). This is achieved by developing a complex computational framework for a coupled pulmonary circulation, left atrium and mitral valve model. The left atrium and mitral valve are modelled with physiologically realistic three-dimensional geometries, fibre-reinforced hyperelastic materials and fluid–structure interaction, and the pulmonary vessels are modelled as one-dimensional network ended with structured trees, with specified vessel geometries and wall material properties. This new coupled model reveals some interesting results which could be of diagnostic values. For example, the wave propagation through the pulmonary vasculature can lead to different arrival times for the second systolic flow wave (S2 wave) among the pulmonary veins, forming vortex rings inside the left atrium. In the case of acute mitral regurgitation, the left atrium experiences an increased energy dissipation and pressure elevation. The pulmonary veins can experience increased wave intensities, reversal flow during systole and increased early-diastolic flow wave (D wave), which in turn causes an additional flow wave across the mitral valve (L wave), as well as a reversal flow at the left atrial appendage orifice. In the case of atrial fibrillation, we show that the loss of active contraction is associated with a slower flow inside the left atrial appendage and disappearances of the late-diastole atrial reversal wave (AR wave) and the first systolic wave (S1 wave) in pulmonary veins. The haemodynamic changes along the pulmonary vessel trees on different scales from microscopic vessels to the main pulmonary artery can all be captured in this model. The work promises a potential in quantifying disease progression and medical treatments of various pulmonary diseases such as the pulmonary hypertension due to a left heart dysfunction.

     

Pulmonary oedema without critical increase in left atrial pressure in acute myocardial infarction.

Twelve patients with acute myocardial infarction and radiological evidence of pulmonary oedema were observed in whom the left atrial pressure, measured indirectly as pulmonary artery end-diastolic pressure, was not critically increased (range 5-12 mm Hg with reference to sternal angle). Eight of the patients had been treated with frusemide, but only six had responded: hence in at least half of the series diuresis could not account for the anomalous finding. Six patients with low cardiac output were given infusions to expand plasma volume. Appreciable increments in mean values for cardiac index (1.6 to 2.0 1/min/m2), stroke index (18 to 23 ml/beat/m2), mean arterial pressure (65 to 86 mm Hg), and pulmonary artery end-diastolic pressure (8 to 15 mm Hg) were recorded. This group, and the remaining six patients with higher cardiac output, survived to leave hospital. Delay in radiographic clearing after a fall of left atrial pressure was a possible explanation for the relatively low pulmonary artery end-diastolic pressures, especially in the patients treated successfully with diuretics. Other mechanisms, such as alterations in pulmonary vascular permeability, might also have contributed to the syndrome. Pulmonary oedema without a critical increase in the left atrial pressure is unusual in acute myocardial infarction but the therapeutic implications are important. Withdrawal;of diuretics may be indicated, and in some cases expansion of plasma volume may lead to striking clinical improvement.     

N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin.

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was elevated with U-46619, intralobar injections of acetylcholine, bradykinin, sodium nitroprusside, isoproterenol, prostaglandin E1 (PGE1), lemakalim, and 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intravenous administration of L-NAME elevated lobar arterial and systemic arterial pressures without altering left atrial pressure. When U-46619 was infused after L-NAME to raise lobar arterial pressure to levels similar to those attained during the control period, vasodilator responses to acetylcholine and bradykinin were reduced significantly, whereas responses to PGE1, lemakalim, and 8-bromo-cGMP were not altered, and responses to nitroprusside were increased. There was a small effect on the response to the highest dose of isoproterenol, and pressor responses to BAY K 8644 and angiotensin II were not altered. These results are consistent with the hypothesis that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine and that EDRF production may have a role in the regulation of tone and in the mediation of responses to acetylcholine and bradykinin in the pulmonary vascular bed of the cat.