Pulmonary vasomotor responses to neural activation in man.

Passive adaptation to changes in flow is an established mechanism of regulation of pulmonary vasomotility. The role of the autonomic nervous system is not well defined in man. To separate the neural from the mechanical component (variation in flow) the venous return and the lung blood flow of six normal men (while undergoing haemodynamic diagnostic procedures) were impeded by a balloon tipped catheter placed in the inferior vena cava. Mental arithmetic and cold pressor tests were used as sympathetic activators. When the venous return was impeded cardiac output was reduced by a mean of 540 ml compared with baseline. During the arithmetic test the rise in cardiac output fell from 2140 ml when venous return was unimpeded to 890 ml when venous return was impeded. This stimulus changed from being a slight pulmonary vasodilator to being an unequivocal vasoconstrictor. Cold stimulation had little effect on cardiac output and caused an increase in pulmonary arteriolar resistance. This effect was more than doubled when flow through the lungs was impeded. These observations suggest that a neural regulation of the pulmonary circulation exists in man, which is disclosed (arithmetic test) or potentiated (cold pressor test) when the influence of mechanical factors is prevented or reduced.

Pulmonary vasoconstrictor overreactivity in borderline systemic hypertension.

Raised vascular pressure and resistance and vasoconstrictor overreactivity to adrenergic stimulation are hallmarks of the pulmonary circulation in sustained primary hypertension. The aim of this study was to investigate the reasons for these disorders. In 10 males with borderline systemic hypertension, pulmonary haemodynamic variables were similar to those of an age matched group of eight normotensive subjects. In normotension, arithmetic and cold pressor tests (sympathetic activators) caused slight vasodilatation and vasoconstriction, respectively. In hypertension both tests showed an obvious vasoconstrictor effect. Restriction of blood flow through the lungs by distension of a balloon in the inferior vena cava is known to increase pulmonary vasoconstrictor reactivity in normal man. As a result of this manoeuvre, pulmonary pressure fell in the normotensive controls without variation in pulmonary vascular resistance, whereas in the hypertensive group there was an increase in resistance and the pressure did not change. In normotensive subjects with caval balloon, the sympathetic activating stimuli both became constrictor and caused vascular resistance to rise to the levels attained in the hypertensive patients during adrenergic stimulation in the absence of obstruction to venous return. In the hypertensives, these stimuli were not able to enhance the pulmonary vascular resistance further. This shows that in these patients maximal vasoconstriction was already achieved through the simple restraint of blood flow with vena caval obstruction. We suggest that in the early phases of systemic hypertension lung vessels are hypercontractile so that they overreact to hypoperfusion or to sympathetic stimulation, even before there is a stable rise in pressure and resistance.

Treatment of hypertension with calcium antagonists. Review.

Calcium channel blockers have a selective action on the cardiovascular system. They reduce the energy requirement of the heart, reduce vascular smooth muscle tone, and increase systemic blood flow. Vasodilatation occurs in both the systemic and the pulmonary systems to an extent proportional to the baseline level of vascular resistance, and results in reduction of blood pressure when it is elevated. Thus, these blockers are useful in patients with high blood pressure. Clinical experience of calcium channel blockers in hypertension is so far confined almost exclusively to verapamil and nifedipine. This article reviews the advantages and limitations of these two compounds, their acute hemodynamic effects in hypertensive subjects, and their use in the treatment of hypertensive emergencies, hypertensive encephalopathy, and pheochromocytoma, and as ventricular afterload reducing agents in hypertensive left ventricular failure. Similarities in the effects of nifedipine on systemic and pulmonary vascular tone are presented as evidence that altered intracellular Ca++ concentration is involved in the vasoconstriction seen in both systems in systemic high blood pressure. They also provide support for the hypothesis that inappropriate Ca++ handling may be involved in maintaining elevated blood pressure in human hypertension.

Nifedipine, a new antihypertensive with rapid action.

Oral (17 cases) or sublingual (9 cases) administration of nifedipine (10 mg), a new coronary dilator, induced a prompt and large pressure reduction in patients with severe primary hypertension. Pressure started to fall within 20 and 5 min after oral and sublingual administration, respectively, and reached the lowest levels in the next 10 min. Maximal mean arterial pressure reduction averaged 36 mm Hg; 120 min after the drug, mean arterial pressure was diminished by 19.5% of control. The hypotension was mediated through diminished peripheral resistance associated with rise of cardiac output and pulse rate. Nifedipine was also administered siblingually in 3 cases with hypertensive encephalopathy and acute left ventricular failure with average systemic and pulmonary arterial pressures from 307/164 and 91/55 mm Hg, respectively, which fell to 237/115 and 68/35 mm Hg 15 min after 10 mg of the drug, and were further reduced to 176/89 and to 47/19 mm Hg by an additional 10 mg.

Medium-term effectiveness of L-thyroxine treatment in idiopathic dilated cardiomyopathy.

BACKGROUND: In dilated cardiomyopathy, short-term administration of L-thyroxine (100 micrograms/ day) improves cardiac and exercise performance without changing the heart's adrenergic sensitivity. The aim of this study was to test the medium-term (3 months) efficacy of L-thyroxine (10 patients) compared with placebo (10 patients) and to find out whether later effects are obtainable. METHODS: Echocardiographic parameters in the control state and during acute changes of left ventricular afterload, cardiopulmonary exercise test, and hemodynamic parameters, including cardiac beta 1 responses to dobutamine, were obtained before and at the end of treatment. RESULTS: Significant (P < 0.05) changes were observed only with the active drug. After L-thyroxine, patients did not show evidence of chemical hyperthyroidism, despite the increase in thyroxine and the reduction in thyroid-stimulating hormone plasma levels. Cardiac performance improved, as shown by the increase in the left ventricular ejection fraction and rightward shift of the slope of the relation left ventricular ejection fraction/end-systolic stress. Resting cardiac output increased, and the left ventricular diastolic dimensions and systemic vascular resistances decreased. The responses of cardiac output and heart rate to dobutamine infusion were also enhanced. Functional capacity markedly improved, together with an increase in peak exercise cardiac output. CONCLUSION: L-thyroxine does not lose its beneficial effects on cardiac and exercise performance on medium-term administration and does not induce adverse effects. In addition to the short-term study, the left ventricular diastolic dimensions were decreased. An upregulation of beta 1 receptors might explain the cardiac response to dobutamine.

Usefulness of L-thyroxine to improve cardiac and exercise performance in idiopathic dilated cardiomyopathy.

The short-term effects of L-thyroxine (100 micrograms/day, 10 patients) and placebo (10 patients) on idiopathic dilated cardiomyopathy were compared. Before and at the end of the treatment, a hemodynamic study was performed in the control state and during dobutamine infusion. A cardiopulmonary exercise test was also performed with hemodynamic monitoring. An echocardiogram was recorded in the control state and during acute changes of left ventricular afterload. Plasma levels of triiodothyronine, thyroxine, thyroid-stimulating hormone and norepinephrine were measured. Placebo was ineffective. After administration of L-thyroxine all patients had normal thyroid function. The increase in left ventricular ejection fraction and the rightward shift of the slope of left ventricular ejection fraction/end-systolic stress relation (p < 0.05) indicated an improvement in the cardiac inotropic state. This proved to be independent of adrenergic influences by the unchanged beta 1 response to dobutamine. A decrease in resting systemic vascular resistances and an increase in cardiac output (p < 0.05) were also observed. Cardiopulmonary effort parameters improved (p < 0.05) without hemodynamic changes at peak exercise. It is concluded that L-thyroxine short-term administration improves cardiac and exercise performance in patients with chronic heart failure, without modifying the adrenergic support to the heart and the circulatory parameters at peak exercise.

Postoperative atelectasis reexpansion by selective insufflation through a balloon-tipped catheter.

Although treatment of refractory atelectasis has been improved by pulmonary insufflation through FOB with balloon cuff, low pulmonary compliance and high critical opening pressure of alveoli in the atelectatic areas require a more selective approach to prevent pressure dispersion to highly compliant zones. To achieve the highest insufflation selectivity and reduce patient discomfort, we have devised a small caliber balloon-tipped catheter to easily reach even the minor branches of the bronchial tree. This result was obtained by utilizing the performed curve of the catheter distal end after withdrawing the internal stylet. The catheter was introduced through the nostrils (16 patients) or through an endotracheal tube (two patients) and advanced under fluoroscopic guidance. Reexpansion of atelectatic areas was accomplished by repeated air injections through a 60-ml syringe. No complications were observed. Complete disappearance of x-ray film evidence of atelectasis was obtained in 15 patients and partial reexpansion in 3 patients.

Systemic to pulmonary bronchial blood flow in heart failure.

STUDY OBJECTIVE: The aim of this study was to measure systemic to pulmonary blood flow from bronchial circulation (Qbr[s-p]) in patients with heart failure. DESIGN: In the absence of pulmonary and coronary flows, Qbr(s-p) is the volume of blood accumulating in the left side of the heart; Qbr(s-p) was measured during total cardiopulmonary bypass for coronary artery surgery; bronchial blood was vented through a cannula introduced into the left side of the heart and its volume was measured. PATIENTS: Patients were subdivided according to the presence for more than 6 months (group 1, n = 6) or less than 2 months (group 2, n = 7), or the absence of heart failure (group 2, n = 15). MEASUREMENTS AND RESULTS: Qbr(s-p) was 89 +/- 18* mL/min, 27 +/- 3, 22 +/- 2, in groups 1, 2, and 3, respectively (* = p < 0.01 group 1 vs groups 2 and 3). During total cardiopulmonary bypass, pulmonary venous pressure approximates atmospheric pressure and no differences between groups were observed in systemic artery pressure, extracorporeal circulation pump flow, and airway pressure. Therefore, vascular resistance through the bronchial vessels draining into the pulmonary circulation is reduced in patients with heart failure for more than 6 months (group 1). CONCLUSIONS: During total cardiopulmonary bypass, Qbr(s-p) is increased in patients with chronic heart failure. Since with elevated pulmonary vascular pressure blood flow through Qbr(s-p) vessels is from the pulmonary to the systemic circulation, the lower resistance observed in group 1 suggests that bronchial vessels might contribute to reduced lung fluid overload in patients with chronic heart failure.

Neural influences on the human pulmonary circulation as a defence reaction to volume depletion.

The role of the autonomic nervous system in the regulation of pulmonary vasomotility in man is unsettled and great emphasis is usually given to changes in flow as the main regulating mechanism. In order to simulate hypovolemia, which might reduce the mechanical influence of flow and disclose a neural mechanism, we decreased venous return through balloon distention in the inferior vena cava in 12 normal subjects, during right heart catheterization performed for diagnostic purposes. Caval obstruction was graduated to reduce cardiac output, right atrial and pulmonary arterial pressures, without altering systemic arterial pressure and heart rate. The sympathetic nervous system was activated by arithmetic and cold pressor tests. During the former, the increase in cardiac output was more than halved by venous return restraint, as compared to the unrestrained condition, and clear pulmonary vasoconstriction, instead of vasodilatation, was observed. During the cold test, cardiac output remained almost steady, in the absence as in the presence of balloon expansion. In both conditions pulmonary arteriolar resistance rose, but in the latter this increase was more than doubled. This study suggests that the autonomic nervous system is involved in the regulation of pulmonary vasomotility in man, its role being unveiled when the mechanical influence of flow is reduced by mimicking a hypovolemic state.

Control of pulmonary vasomotility in congestive heart failure.

Although enhanced sympathetic tone is a well-known component of the autonomic imbalance of heart failure, its influence on pulmonary vasomotility is undefined. We investigated the pulmonary circulation in 12 patients with congestive heart failure in NYHA functional class III and in a control group of 10 normal subjects. Sympathetic influence on pulmonary vessels was studied through adrenergic activation by the arithmetic test and the cold pressor test. A rubber balloon was distended in the inferior vena cava to reduce transpulmonary flow and its influence on vascular tone. In normal individuals the arithmetic test caused pulmonary vasodilation, probably because of the mechanical effect of a largely enhanced flow: in fact, caval obstruction unmasked a neurogenic vasoconstrictor response to the arithmetic test by simply reducing the amount of cardiac output increase. In patients with heart failure, cardiac output and pulmonary arteriolar resistance remained steady during the arithmetic test, no matter what the condition of the venous return was. The cold pressor test was always a vasoconstrictor stimulus, but only in normal subjects was vasoconstriction potentiated by reducing, with caval obstruction, transpulmonary flow and its vasodilatory influence. From these data an attenuation of the sympathetic influence on pulmonary vessels in congestive heart failure seems to be likely. This might be explained as the result of modifications of pulmonary vessels rather than of reduced sympathetic excitability since circulating catecholamine levels varied to similar extents in the two groups during the tests. In congestive heart failure interstitial edema and vascular wall imbibition might increase pulmonary vessel tone and decrease vascular receptor availability. Lower reactivity to sympathetic stimuli, particularly to the vasoconstrictor ones, would ensue.

Echocardiographic and hemodynamic correlates in Prinzmetal angina pectoris: a case report.

In a patient suffering from Prinzmetal angina pectoris, ischemic attacks of the anterior left ventricular wall were associated with the following changes: fall in cardiac output; increased left ventricular diastolic pressure (LVDP) and volume; flattening of the septal motion; marked reduction of the mitral valve early diastolic amplitude and rate of opening; and marked reduction of the systolic closure velocity. It is suggested that LVDP rise depends, at least in part, on variations in left ventricular diastolic volume and segmental wall motion, and that disruption of the mitral valve motion derives from changes in LVDP and flow through the mitral orifice.

Calcium channel blockade with nifedipine reduces the systemic and the pulmonary vascular reactivity to adrenergic activation in hypertension.

In hypertension the systemic and the pulmonary circulation show exaggerated vascular tone and responsiveness to adrenergic stimuli. In 22 hypertensive men we tested whether the regulation of the two vascular beds is improved by calcium entry blockade with nifedipine. Mental arithmetic raised epinephrine plasma concentration (by 80%), cardiac output (CO) and blood pressure in both circuits, and caused systemic vasodilatation and pulmonary vasoconstriction. After the drug the epinephrine reaction was diminished (+20%), variations in CO and systemic blood pressure were almost unchanged and pulmonary vasoconstriction was abolished. A cold pressor test increased norepinephrine plasma concentration (by 24%), systemic and pulmonary pressure and resistance and did not alter CO. The norepinephrine response to cold was enhanced (+35%) by nifedipine, while systemic and pulmonary resistance rises were importantly attenuated (from +24% to +7% and from +41% to +1%, respectively), and greatly diminished the pressure reactivity. A sympatho-adrenal modulation by calcium blockade, per se, might have restrained the vasomotion during arithmetic. The impressive attenuation of the constrictor responses to cold, which was possibly associated with a potentiated sympathetic drive, prospects that the two circuits share a vascular contractile disorder in which calcium ions are involved.

[Neural influences on pulmonary vasomotility in man]. / Influenze nervose sulla vasomotilità polmonare nell'uomo.

In man, the extent, the physiological role and even the existence of neural influences on the pulmonary vasomotility are not defined. A major obstacle to these evaluations is passive adaptation of the lung vessels to changes in flow, making it hard to separate the active from the passive component of vasomotion during adrenergic activation. In this study, which was carried out in 8 patients during diagnostic procedures, the inflation of a balloon in the inferior vena cava was utilized to reduce blood flows through the lungs and to buffer its changes consequent to stimulation of the adrenergic system. Neural activation was obtained with the mental arithmetic and the cold pressor tests. When venous return was unimpeded, cardiac output rose by 2,060 ml during the former and remained stable during the latter test, and arteriolar resistance in the pulmonary circuit was significantly reduced and slightly increased, respectively. Under vena cava obstruction, cardiac output decreased in the baseline by 600 ml; it rose by 925 ml during the arithmetic test and again remained stable during the cold test; pulmonary arteriolar resistance was unchanged since before obstruction in the baseline and was significantly augmented by both test. These observations support the view that lung blood vessels in man are sensitive to adrenergic influences and the vasoconstrictor component of these becomes effective in circumstances in which the flow through the lungs reduced. The physiological importance of these influences remains unclear.

Neural influences on the pulmonary vascular bed in man.

1. Impedance to venous return by distention of a balloon in the inferior vena cava (IVCB) was utilized in 10 patients, during diagnostic procedures, to reduce blood flow through the lungs at baseline and to buffer its changes during stimulation of the adrenergic system, which was obtained with mental arithmetic (AT) and cold pressor (CPT) tests. 2. When venous return was unimpeded, cardiac output rose by 2.06 1/min during the AT and remained steady during the CPT, and arteriolar resistance in the pulmonary circuit was significantly reduced and slightly raised, respectively. 3. During IVCB, baseline cardiac output decreased by 710 ml/min, it rose by 925 ml/min during the AT and again remained steady during the CPT; pulmonary arteriolar resistance was unchanged from before obstruction at baseline and was significantly augmented by both tests. In particular, AT became a clear vasoconstrictor stimulus, having originally produced vasodilatation. 4. These observations support the view that lung blood vessels in man are sensitive to adrenergic influences and that vasoconstriction can be elicited in circumstances in which the flow through the lungs is restrained. The physiological importance of the neural regulation of the pulmonary circulation in man remains undefined.

Sleep apnoea in ischaemic heart disease: differences between acute and chronic coronary syndromes.

OBJECTIVE: To evaluate the incidence of sleep apnoea in acute and chronic coronary syndromes. DESIGN: Analysis of sleep and breathing characteristics in a polysomnographic study. SETTING: Cardiology department in tertiary referral centre. PATIENTS: 23 patients were studied soon after acute myocardial infarction (group 1), 22 after clinical stabilisation of unstable angina (group 2), and 22 who had stable angina (group 3). Conditions liable to cause sleep apnoea, such as obesity, chronic obstructive pulmonary disease, neurological disorders, or the use of benzodiazepines, were exclusion criteria. MAIN OUTCOME MEASURES: Sleep apnoea and hypopnoea, oxygen saturation, and sleep indices evaluated soon after clinical stabilisation in groups 1 and 2 and also in group 3. RESULTS: Sleep apnoea, mainly of the central type, was equally present in groups 1 and 2 (mean (SD) apnoea-hypopnoea index: 11.10 (19.42) and 14.79 (20.52), respectively) and more severe than in group 3 (2.82 (6.43), p < 0. 01). Total time spent at SaO(2) < 90%, although significantly greater in group 1 and 2 (0.89 (2.4), 1.42 (3.23) min) than in group 3 (0.01 (0.05) min, p < 0.05), was clinically irrelevant. More arousals per hour of sleep (p < 0.05) were detected in group 1 (5.15 (3.71)) and group 2 (5.31 (2.14)) than in group 3 (2.83 (1.51)). CONCLUSIONS: Sleep apnoea, chiefly of the central type, not only characterises acute myocardial infarction, as found by others, but also unstable angina studied after recent stabilisation. Patient selection by exclusion of other causes of breathing disorders shows that coronary disease related apnoea is absent in the chronic coronary syndrome. In acute syndromes the lack of clinically significant apnoea related oxygen desaturation, together with the low associated incidence of major ischaemic and arrhythmic events, suggests that sleep apnoea is benign in these circumstances, despite a worsening of sleep quality.

[Changes in pulmonary vascular reactivity to adrenergic stimuli in congestive heart failure]. / Modificazioni della reattività vascolare polmonare agli stimoli adrenergici nello scompenso cardiaco congestizio.

Heart failure is associated with increased activity of sympathetic nervous system. As to the latter's effector organs, attention has been mainly drawn by heart and systemic circulation. In this study we investigated whether and how the neurogenic vasomotility of the lesser circulation is modified. Therefore, we compared 12 patients with heart failure in III NYHA functional class, with 10 subjects, undergoing hemodynamic study for diagnostic reasons and found to be normal. The neurogenic reactivity of pulmonary vessels was assayed by means of 2 sympathetic stimuli: arithmetic test (AT) and cold pressor test (CPT), performed both with and without obstruction to right heart venous return. This was obtained by expanding a balloon in inferior vena cava, in order to rid the neurogenic component of pulmonary vasomotility of the interference of the normally prevailing mechanical component (consisting in adaptations to flow variations). AT caused pulmonary vasodilation in normal subjects, as a passive consequence of the increase of cardiac output and, therefore, of pulmonary flow. Caval obstruction, by simply restraining this increase, induced a clearly neurogenic vasoconstrictor response. On the contrary, in failing patients, a slight vasodilation, independently from the condition of venous return, was observed. This took place in spite of the constant absence of any variations of cardiac output, which both indicates the reduction of myocardial function and helps to show the diminished nervous influence on pulmonary circulation. On the other hand, CPT had a vasoconstrictor effect in both groups, though potentiated by the reduction of transpulmonary flow in normal subjects only.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic and haemodynamic correlates in supraventricular tachycardia.

In 16 subjects with paroxysmal supraventricular tachycardia (SVT) we sought a relationship between haemodynamic changes associated with artificially induced arrhythmias and the electrophysiological properties of the related atrioventricular (AV) nodal reentry circuit. In 10 patients (group 1) induced SVT was typical (long AH) and caused a significant fall in cardiac output (-1.720 ml min-1) and arterial systolic pressure (-18 mmHg). In six subjects (group 2), induced SVT was atypical (long HA) and did not significantly alter the output of the heart and systolic pressure, despite the elicitation of similar tachycardia. The opposite AV nodal reciprocation pattern which resulted in a substantial increase in AH/HH in group 1 and in a slight rise of the same variable in group 2, may explain these haemodynamic differences. In fact, atrial and ventricular systoles occurred simultaneously and impeded the ventricular filling in the former group, while a regular subsequence of contraction was maintained in the latter group. In group 2, systolic arterial pressure and cardiac output fell to the same level as in group 1 when right atrial pacing, at a similar rate of SVT, determined an increase of AH/HH similar to that observed during typical tachycardia. Thus, the haemodynamic response to SVT differs significantly between the two types of reciprocating tachycardia, particularly as regards cardiac output and blood pressure, and is mainly influenced by the temporal relationship between atrial and ventricular systole, independent of the rate of contraction. The different conduction velocities of the reciprocating circuit limbs and their interrelation seem to be major determinants of the haemodynamic pattern of SVT.

Obstruction of the right pulmonary artery by an aortic aneurysm complicating previous coronary bypass grafting.

We report a case of right main pulmonary artery compression due to a type II dissecting aortic aneurysm simulating massive pulmonary artery embolism. Aortic tear and intimal splitting developed around an aortocoronary bypass graft performed 11 months earlier. Ultrasound detected the aortic aneurysm and pulmonary hypertension, and excluded emboli in the pulmonary artery. Pulmonary angiography explained the lung involvement, showing compression of the right main pulmonary artery. Coronary and aortic angiograms demonstrated that the aortic aneurysm developed around the right venous bypass graft. Surgery confirmed the angiographic findings and the pathogenesis of the syndrome.

The lesser circulation in patients with systemic hypertension.

The elevated blood pressure and vascular resistance in patients with systemic hypertension are paralleled by a proportional rise in pressure and resistance in the lesser circulation. We evaluated the hypothesis that the increased systemic reaction to adrenergic stimulation is shared by the pulmonary vessels. For this purpose we investigated nine normotensive subjects and 24 patients with moderate primary hypertension during mental arithmetic and the cold pressor test. Both groups responded to both stimuli, with a pressure reaction that during arithmetic was mediated through an increase of cardiac output, and a reaction during the cold pressor test mediated through a predominant rise in systemic vascular resistance. The pressure changes were emphasized in the hypertensive population. Pressure in the pulmonary artery in normotensive subjects was not affected by cold and was slightly raised (systolic) during arithmetic. In hypertensive patients, on the other hand, systolic and diastolic pressures were consistently augmented by both tests, and pulmonary arteriolar resistance rose by 42% and 29% of control during the cold pressor test and arithmetic, respectively. Changes in resistance reflected neurally mediated vasoconstriction and not variations in the passive relationship between pressure and flow, since during arithmetic, for a similar rise in flow the driving pressure across the lungs was steady in normotensive subjects and rose significantly in hypertensive patients. In these same patients pressure was augmented by cold in the absence of substantial changes in flow. At baseline and during tests pulmonary wedge pressure, pleural pressure, arterial blood gases, and pH were similar in the two populations.(ABSTRACT TRUNCATED AT 250 WORDS)