Modulation of sympathetic coronary vasoconstriction by cardiac renin-angiotensin system in human coronary heart disease.

Background: In humans, angiotensin II enhances the sympathetic coronary vasoconstriction elicited by the cold pressor test (CPT) and diving. Whether this enhancement depends on the circulating angiotensin II or on the locally produced angiotensin II is unknown, however.

Methods And Results: We addressed this issue in 14 patients with severe coronary artery disease by evaluating the effects of a 2-minute CPT (n=14) and a 30-second dive (n=8) on mean arterial pressure (MAP, arterial catheter), heart rate (ECG), coronary sinus blood flow (CBF, thermodilution technique), and coronary vascular resistance (MAP/CBF ratio).

Exercise-induced paroxysmal atrioventricular block during nuclear perfusion stress testing: evidence for transient ischemia of the conduction system.

Background: Whether tachycardia-dependent paroxysmal AV block, an uncommon complication of exercise stress testing in patients with infranodal conduction disturbances, can result from acute ischemia of the conduction system is still speculative, and is based on post-hoc evidence of right coronary artery disease and abolition of block after coronary angioplasty.

Methods And Results: In two patients, from a database of 3000 undergoing nuclear exercise stress testing, transient paroxysmal AV block developed 1-4 minutes after the injection of the radionuclide agent. Nuclear perfusion imaging demonstrated stress-induced ischemia of the posteroseptal segments, which corresponds to the anatomical region of the His bundle, and perfusion recovery in the images obtained at rest.

Treatment of Helicobacter pylori and Chlamydia pneumoniae infections decreases fibrinogen plasma level in patients with ischemic heart disease.

Background: Chronic Chlamydia pneumoniae and Helicobacter pylori infections could be a risk factor for ischemic heart disease (IHD), possibly by increasing fibrinogen levels. The aim of our study was to evaluate changes in fibrinogen level in patients with IHD and H pylori and/or C pneumoniae positivity randomly assigned to antibiotic treatment.

Methods And Results: Eighty-four patients with chronic IHD, H pylori and/or C pneumoniae antibodies, and normal acute-phase reactants were randomly assigned to treatment or no treatment.

An improved method for coronary sinus blood flow monitoring by intravascular Doppler technique.

In order to obtain accurate measurements of coronary sinus blood flow (CSBF), a new catheter (7 French) with a radiopaque, flexible, and basket-shaped tip was developed for guiding a standard 3 Fr Doppler catheter in the coronary sinus (CS) in man. The radiopaque "basket" tip of the catheter allows the operator to stabilize the position of the Doppler transducer in the center of the CS and to accurately measure the CS internal diameter radiologically. CSBF was calculated as the product of CS cross-sectional area by mean CSBF velocity.

Intracoronary angiotensin II potentiates coronary sympathetic vasoconstriction in humans.

Background: In humans with coronary artery disease, ACE inhibition attenuates coronary sympathetic vasoconstriction. Whether this is due to removal of angiotensin (Ang) II production or to a reduced bradykinin breakdown, however, is unknown.

Methods And Results: In eight normotensive patients with angiographic evidence of mild left coronary artery lesions (< or = 50%), mean arterial pressure (MAP, intra-arterial catheter), heart rate (HR, ECG lead), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between MAP and CBF) were measured before and during a 15-minute left intracoronary infusion of Ang II at a dose that had no direct coronary or systemic vasomotor effects.

Effects of amlodipine on coronary hemodynamics and vascular responses to sympathetic stimulation in patients with coronary heart disease.

Dihydropyridines (DHPs) exert a powerful coronary vasodilator action, but whether they actually affect the coronary vasomotor effects elicited by an increase in cardiac sympathetic drive is controversial. We assessed the effects of the DHP calcium antagonist amlodipine on coronary hemodynamics and vascular response to sympathetic activation in patients with coronary heart disease. In the control condition, mean arterial pressure (MAP, aortic catheter), heart rate (HR, ECG), rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution) and coronary vascular resistance (CVR) (ratio between MAP and CBF) were measured in all our case series (13 patients with angiographically documented severe coronary artery disease) before and during a 2-min cold pressor test (CPT) and a 30-s diving (D) and, in the 8 patients of this case series who were smokers, also before and during smoking a cigarette (S, nicotine content 1.

Coronary vascular reactivity and calcium antagonist therapy in patients with angina.

In patients with severe coronary atherosclerotic disease, the angiotensin-converting enzyme inhibitor captopril attenuates the vasoconstriction induced by the cold pressor test and diving (two stimuli that cause reflex sympathetic activation) via removal of the facilitating effect of angiotensin II on sympathetic drive. However, whether calcium antagonists also have this effect is not clear. We evaluated the effects of a single 11-mg intravenous dose of the dihydropyridine calcium antagonist amlodipine on the coronary vascular response to the cold pressor test, a 30-s application of the dive reflex and cigarette smoking (whose effects on the coronary circulation also involve the sympathetic nervous system).

Impairment of the arterial baroreflex during symptomatic and silent myocardial ischemia in humans.

Objectives: The aim of this study was to assess whether transient episodes of symptomatic or silent myocardial ischemia after baroreceptor modulation of heart rate.

Background: Animal and human studies have shown that myocardial infarction is accompanied by an impairment of the baroreceptor influences on the sinus node. However, whether this also occurs during transient myocardial ischemia has never been documented.

RAA system and cardiovascular control in normal subjects, hypertensives and patients with congestive heart failure.

The involvement of the renin-angiotensin-aldosterone (RAA) system, particularly angiotensin II, in the pathogenesis of hypertension is widely acknowledged and is supported by several observations: the RAA system has been shown to be critically involved in the development of some experimental hypertensions; activation of the RAA system appears to be the crucial factor involved in the maintenance of the BP elevation in some antihypertensive patients; while drugs which interfere with the production of angiotensin II reduce BP in a large number of hypertensive patients. It is now clear that the chronic BP elevations caused by circulating (and perhaps locally produced) angiotension II may have adverse effects on organ function and protection: for example, induction of cardiac hypertrophy and vascular hypertrophy and/or hyperplasia, reduction of arterial compliance and reduction in vagal tone and facilitation of sympathetic activity on cardiac and vascular targets. At the cardiac level, the renin-angiotensin sympathetic interaction may enhance electrical instability, thereby favouring arrhythmias and increasing mortality after a myocardial infarction.

ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease.

Background: In humans, angiotensin converting enzyme (ACE) inhibition attenuates the vasoconstriction induced by sympathetic stimulation in a number of peripheral districts. Whether this is also the case in the coronary circulation is unknown, however.

Methods And Results: In nine normotensive patients with angiographically assessed coronary atherosclerosis, we measured the changes in mean arterial pressure (intra-arterial catheter), heart rate, rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between mean arterial pressure and CBF) induced by the cold pressor test (CPT, 2 minutes) and diving (30 seconds), i.

Coronary response to diving in subjects with mild and severe left coronary artery disease.

The cold pressor test (CPT) is commonly used to determine the vasospastic origin of angina and to investigate the factors modulating coronary vasomotor tone. However, coronary vasoconstriction associated with this manoeuvre is often limited, particularly in patients with mild coronary atherosclerosis. To identify stimuli that can more powerfully constrict the coronary arteries we compared the effects on coronary blood flow (thermodilution) and vascular resistance (mean aortic pressure divided by coronary blood flow) of CPT (2 min) and diving (D, 45 s) in subjects with angiographically documented mild (n = 11) or severe (n = 11) left anterior descending coronary artery stenosis.

Effect of oral dilevalol on forearm circulation in essential hypertension.

In 7 patients with untreated mild essential hypertension, a single 200-mg dilevalol dose was administered orally. Blood pressure (BP, left brachial artery catheter), heart rate (HR), and left and right forearm blood flows were measured and left and right forearm vascular resistances were calculated before and for approximately 3 h after drug administration. Dilevalol administration was followed by a sustained reduction in BP, little change in HR, and a similar pronounced and sustained increase in left and right forearm blood flows and reduction in left and right forearm vascular resistances.

Use of intravenous digital subtraction ventriculography in the evaluation of left ventricle volumes and ejection fraction.

Although intravenous digital subtraction ventriculography (IDSV) is increasingly used to estimate end-diastolic left ventricular volume (EDV), end-systolic left ventricular volume (ESV) and left ventricular ejection fraction (EF), its ability to reproduce the precise estimates provided by left ventricle cineangiography (LVCA) and its role in clinical cardiology have not been unequivocally established. In 32 patients subjected to cardiac catheterization for a variety of cardiac disorders and a normal or reduced left ventricular function the EDV, ESV and EF provided by a 30 degrees right anterior oblique LVCA were compared with those provided by a 30 degrees right anterior oblique IDSV. The mean EDV, ESV and EF obtained by IDSV in the 32 patients were superimposable on those obtained by LVCA.

Haemodynamic effects of ACE inhibitors.

This paper reviews the haemodynamic effects of angiotensin-converting enzyme (ACE) inhibitors in hypertension, focusing on their ability to cause a fall in systemic vascular resistance, with no change in cardiac output and no reduction and even an increase in blood flow to vital organs such as the brain, the kidney and the heart. The haemodynamic effects of ACE inhibitors are qualitatively similar in congestive heart failure, except that, in the presence of impaired cardiac function, the fall in resistance is accompanied by a pronounced increase in cardiac output and tissue perfusion. In both conditions ACE inhibition opposes sympathetic influences and enhances vagal influences and, in hypertension, this intervention is followed by a regression of left ventricular hypertrophy providing a multifold background for a cardioprotective action.

Calcium antagonists and neural control of circulation in essential hypertension.

Data from animals and from man suggest that calcium antagonists interfere with alpha-adrenergic receptors and that this mechanism may be responsible for some of the vasodilation induced by these drugs. However, alpha-adrenergic receptors play a primary role in baroreceptor regulation of the cardiovascular system and blood pressure homeostasis, which might therefore be adversely affected by calcium antagonist treatment. We addressed this question in 14 essential hypertensives studied before treatment, 1 h after 20 mg oral nitrendipine and 5-7 days after daily administration of 20 mg oral nitrendipine.

Effects of altering the interval between the stimulus and the reflex response in the analysis of the baroreceptor control of the sinus and atrioventricular nodes in man.

Baroreceptor control of the sinus node may be determined by raising or lowering blood pressure with intravenous bolus injections of phenylephrine or glyceryl trinitrate and calculating the slope of the linear regression between the drug induced changes in systolic blood pressure and RR interval using shift 1 coupling--namely, coupling of each systolic blood pressure value with the interval of the following cardiac cycle. To assess whether shift 1 coupling provides the best linear fit and the highest regression slope nine subjects received phenylephrine and glyceryl trinitrate injections both during spontaneous sinus rhythm and during atrial pacing to evaluate baroreflex control of the sinus and of the atrioventricular node respectively. In regression analysis of the data, for each drug injection nine different shifts (from 0 to 8) were used to couple systolic blood pressure with RR or StQ intervals.

Hemodynamic effects of acute and prolonged administration of nitrendipine in essential hypertension.

In six hospitalized subjects with mild or moderate and untreated essential hypertension, we measured mean blood pressure (MBP, brachial artery catheter), heart rate (HR, electrocardiogram), cardiac output (CO, thermodilution), and total peripheral resistance (TPR, MBP divided by CO) at rest and during a cold pressor test (CPT, 60 s), a hand-grip exercise (HG, 40% maximum strength for 90 s), and a cyclette exercise (CE, 50 W for 5 min). The study was performed in a no-drug condition, 1 h after 20 mg oral nitrendipine (aN) and 1 week after daily administration of 20 mg oral nitrendipine (pN). Compared with the no-drug condition, aN reduced resting MBP from 137.

Informative value of simple multibreath nitrogen washout measurements for clinical and research purposes.

Some simple multibreath nitrogen washout indexes quantifying inspired gas distribution and ventilatory efficiency were obtained in a group of patients with mild to advanced chronic obstructive pulmonary disease (COPD) and studied in their relationships with routine pulmonary function tests. The indexes (lung clearance index (LCI), mixing ratio (MR) and data obtained by graphic analysis of the washout curve) were correlated with spirometric, pulmonary mechanics and arterial blood gas measurements, but only 8-38% of the interindividual variation in these indexes was explained by the above routine tests. An additional 5-13% of the variation was explained by the washout tidal volume (VT); this finding may reflect changes in gas distribution with VT and/or the influence of the dead space on ventilatory efficiency.

Modification of the baroreceptor control of atrio-ventricular conduction induced by digitalis in man.

Several studies in animals and in man have suggested that the inhibitory influence of baroreceptors on heart rate and peripheral circulation is enhanced by digitalis. Because the atrio-ventricular node represents a key site for the clinical action of digitalis we studied how baroreceptor control of atrio-ventricular conduction is modified by digitalis at therapeutical doses. In eight subjects heart rate was kept constant by atrial pacing to assess neural influences on atrio-ventricular conduction rate without the modifications caused by simultaneous changes in cardiac cycle length.

Pulmonary resistance and dynamic compliance as functions of respiratory frequency.

The behavior of pulmonary resistance (RL) and that of dynamic compliance (Cdyn) as functions of respiratory frequency (f) were compared in normal subjects and in patients with chronic obstructive pulmonary disease (COPD). Although both RL and Cdyn varied with f in most COPD patients and in some normal subjects, Cdyn appeared to be more sensitive than RL to variations of frequency; no significant changes in RL could be demonstrated in subjects in whom Cdyn was frequency dependent. The degree of frequency dependence of Cdyn was correlated with the severity of respiratory impairment (as quantified by conventional pulmonary function tests); in contrast, RL was not detectably frequency dependent in some subjects with advanced COPD.

Hypocapnia and measurement of airflow resistance and dynamic compliance as functions of respiratory frequency.

Measurements of lung mechanical behaviour as a function of respiratory frequency may be associated with significantly increased ventilation at high breathing rates. It follows that these measurements may be influenced by hypocapnia which has been shown to increase airflow resistance and to decrease dynamic compliance. To examine this possibility we continuously monitored the end-tidal CO2 tension during the determination of pulmonary resistance and dynamic compliance as functions of frequency and we compared measurements obtained by the standard method and by a technique designed to prevent the development of hypocapnia at high breathing rates.

Effects of bronchodilators on the behavior of pulmonary resistance and dynamic compliance as functions of respiratory frequency.

The effects of bronchodilator treatment (intravenous atropine or inhaled metaproterenol) on the behavior of pulmonary resistance (RL) and dynamic compliance (Cdyn) as functions of respiratory frequency were studied in patients with chronic obstructive pulmonary disease and in apparently normal smokers. No systematic changes in the frequency-dependent behavior of RL and Cdyn were observed after bronchodilator treatment; the degree of frequency dependence increased in some subjects, and decreased or remained unchanged in others. The present results suggest that the effects of bronchodilators on the relationships between lung mechanical properties and respiratory frequency are not based on a single mechanism, but probably reflect the interaction of multiple factors possibly associated with the bronchodilator treatment.

Exercise and distribution of inspired gas in patients with obstructive pulmonary disease.

The effects of moderate exercise on the distribution of inspired gas and efficiency of ventilation were studied by the multibreath nitrogen washout method in three subjects with asymptomatic asthma and 11 patients with chronic obstructive pulmonary disease (COPD). The nitrogen washout curves were analyzed according to a lung model consisting of a poorly ventilated compartment (slow space) and one or more better ventilated compartments (intermediate and fast compartments). The overall efficiency of ventilation was also estimated by the lung clearance index (LCI).