Rodolfo Perondi

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

BackgroundIn 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 ResultsIn 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.e., two stimuli eliciting a sympathetic coronary vasoconstriction. The measurements were performed in the control condition and 30 minutes after captopril 25 mg p.o. In the control condition, CPI caused an increase in mean arterial pressure and heart rate. Despite the increase in RPP (+20.7±3.2%, p<0.01), CBF did not change and CVR increased (+12.2±4.0%, p<0.05); diving caused an increase in mean arterial pressure and a reduction in heart rate. RPP increased (+14.3±3.5%, p<0.01), but despite this increase, there was a reduction in CBF and a marked increase in CVR (+37.3±7.4%, p<0.01). Captopril did not modify the blood pressure and heart rate responses to both stimuli except for a slight accentuation of the bradycardia to diving. Despite the unchanged or only slightly reduced RPP response, the increase in CVR was markedly and significantly attenuated (p<0.01). ConclusionsACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. This is probably due to removal of the facilitating influence of angiotensin II on sympathetic modulation of coronary vasomotor tone.

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. The same measurements were made before and during a 15-minute infusion of saline. A 2-minute cold pressor test (CPT) and a 45-second diving were performed at the end of either infusion period. These maneuvers were used because their coronary vasomotor effects are abolished by phentolamine and thus depend on sympathetic activation. During saline infusion, both CPT and diving caused a marked increase in MAP. HR increased with CPT and fell with diving. CBF increased in parallel to the MAP increase, with little change in CVR. The MAP and HR responses were similar during Ang II infusion, which, however, caused either no change or a reduction in CBF with a consequent marked increase in CVR with both CPT and diving. In four additional patients, the diameter of the stenotic vessels remained unchanged during the CPT performed under saline and Ang II infusion. CONCLUSIONS Ang II markedly enhances sympathetic influences on coronary circulation in humans, presumably by acting at the arteriolar level. This may explain the blunting effect of ACE inhibition on sympathetic coronary vasoconstriction in patients with coronary artery disease.

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). The 2 stimuli were applied at the end of left intracoronary infusion of either saline or benazeprilat diluted at the concentration of 25 microgram/mL. The rate of benazeprilat infusion had been preliminarily demonstrated to reduce angiotensin II concentration in the coronary sinus without affecting its arterial concentration. The changes in MAP and heart rate induced by CPT and diving were superimposable during saline and benazeprilat infusions. The decrease in CBF induced by CPT and diving during saline infusion was changed into an increase during benazeprilat infusion with a significant attenuation of the coronary vasoconstrictor response. CONCLUSIONS In patients with coronary artery disease, an attenuation of sympathetic coronary vasoconstriction can be obtained by reducing cardiac angiotensin II formation without involving circulating angiotensin II. This suggests a role of the tissue renin-angiotensin system in modulating autonomic cardiac drive in humans.

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. METHODS In 12 patients undergoing coronary angiography, systolic blood pressure (intraarterial catheter) was reduced by an intravenous bolus of nitroglycerin during a spontaneous episode of transient chest pain and myocardial ischemia (ST segment depression on the electrocardiogram) and 30 min after recovery. The slope of the linear regression between the decrease in systolic blood pressure and the RR interval shortening was taken as the measure of baroreflex sensitivity. RESULTS During ischemia, baroreflex sensitivity was 1.3 +/- 0.3 ms/mm Hg (mean +/- SEM), whereas after recovery it was markedly and significantly greater (2.6 +/- 0.5 ms/mm Hg, p < 0.01). Similar results were obtained in eight other patients who experienced a silent ischemic episode either spontaneously or during coronary angioplasty. The reduction in baroreflex sensitivity was similarly pronounced during inferior (10 patients) and anterior (10 patients) ischemia, and its magnitude showed little or no relation to the ischemia-dependent changes in blood pressure and heart rate. CONCLUSIONS Transient myocardial ischemia is associated with marked baroreflex impairment. The impairment occurs even during symptomless ischemic episodes and is therefore not related to pain or to other nonspecific influences on the baroreflex.

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. Our data indicate that, in patients with COPD, nitrogen washout indexes tend to change in parallel with routine pulmonary function tests, reflecting the severity of the disease; these indexes also contain specific information (in addition to that provided by routine physiologic tests), presumably related to the distribution and efficiency of ventilation. Nitrogen washout measurements may thus represent a helpful adjunct to routine pulmonary function testing; LCI and MR appear to be particularly convenient for practical purposes because of their simplicity, and an informative content comparable with that of more complex indexes.

Effects of an inhaled bronchodilator on gas distribution and over-all ventilatory efficiency in patients with chronic obstructive pulmonary disease

The effects of an inhaled bronchodilator on the distribution of inspired gas and over-all efficiency of ventilation were studied by the nitrogen washout technic in 16 patients with chronic obstructive pulmonary disease; three normal subjects and two patients with asymptomatic asthma (and normal spirometric values) were also studied. In normal and asthmatic subjects and in patients with chronic obstructive pulmonary disease and mild to moderate functional impairment, the nitrogen clearance did not vary significantly or showed changes suggesting less uniform gas distribution and reduced ventilatory efficiency. In most patients with advanced chronic obstructive pulmonary disease, the bronchodilator caused changes suggesting more uniform distribution of inspired gas and increased efficiency of ventilation. Multiple regression analysis showed that the behavior of the nitrogen clearance after treatment was also related to the response of the anatomic dead space. The effects of the bronchodilator varied with time. The results are consistent with the assumption that the changes in nitrogen clearance after bronchodilator therapy reflect the concourse of multiple factors, which may be expected to have favorable or unfavorable effects on the distribution of inspired gas and the efficiency of ventilation.

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 137.3 +/- 7.3 (mean +/- SEM) to 112.3 +/- 9 mm Hg (p less than 0.05), increased resting HR from 72.3 +/- 6.9 to 85.3 +/- 8.8 beats/min) (p less than 0.05), increased resting CO from 6,191 +/- 508, to 8,700 +/- 1,050 ml/min (p less than 0.05), and reduced resting TPR from 1,807 +/- 119 to 1,140 +/- 228 dynes/s/cm5 (p less than 0.05). The reduction in resting MBP and TPR were unchanged by pN, whereas the increase in HR and CO were attenuated by 47 and 42%, respectively (p less than 0.05). Neither aN nor pN altered the hemodynamic responses to CPT, HG, and CE. As a result, the peak MBP and TPR values that were measured during these maneuvers were always lower (p less than 0.05) during aN and pN than in the no-drug condition. Thus, nitrendipine exerts marked antihypertensive and vasodilatatory effects that are evident at rest and during conditions elevating BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of oral dilevalol on forearm circulation in essential hypertension

Summary: 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 ˜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. At the end of the observation period, the changes in left forearm circulation were unaffected by left brachial artery infusion of saline but markedly reduced by left brachial artery infusion of propranolol at doses that had no effect on BP, HR, and contralateral forearm vasodilatation. Thus, at an oral dose exerting an antihypertensive effect, dilevalol induces a marked and persistent vasodilation due largely to the β-adrenoceptor agonism of the drug.

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.