Trends in severe outcomes in SARS-CoV-2-positive hospitalized patients with rheumatic diseases: a monocentric observational and case-control study in northern Italy.

Rheumatic disease patients are at greater risk of infection due to their disease, comorbidities, and immunosuppressive therapy. COVID-19 outcomes in this patient setting appeared to be similar to those of the general population. However, data on this topic were mainly related to small studies on a limited number of patients. Consequently, to date, this field remains poorly explored, particularly in the pre-vaccine era. This monocentric study aimed to describe the intrahospital mortality in rheumatic patients with SARS-CoV-2 consecutively hospitalized from 21 February to 31 December 2020, before anti-SARS-CoV-2 vaccine administration spread, compared with non-rheumatic patients. Of 2491 included patients, 65 [3%, median (interquartile range) age 75 (64.76-82.239 years, 65% women] were suffering from rheumatic diseases. A total of 20 deaths were reported [case fatality rate 31%, 95% confidence interval (CI): 19-42] compared with 433 deaths (19%, 95% CI: 17-20) in patients without rheumatic diseases (p=0.024). However, the rheumatic disease was not associated with a significant increase in univariate mortality hazards (hazard ratio 1.374, 95% CI: 0.876-2.154), and after adjustment (hazard ratio 1.199, 95% CI: 0.759-1.894) by age, sex and Charlson comorbidity index. The incidence of intensive care unit admission, death, and discharge in the case-control study was comparable between rheumatic and non-rheumatic patients. The presence of rheumatic diseases in SARS-CoV-2-hospitalized patients did not represent an independent risk factor for severe disease or mortality.

Role of cardiovascular magnetic resonance in suspected cardiac amyloidosis: late gadolinium enhancement pattern as mortality predictor.

BACKGROUND: Cardiac magnetic resonance (CMR) has gained a central role in the diagnosis of cardiac amyloidosis (CA). While the diagnostic role of a typical late gadolinium enhancement (LGE) pattern (global subendocardial enhancement coupled with accelerated contrast washout) has been identified, evidence is still conflicting regarding the prognostic role of such examination. METHODS AND RESULTS: We retrospectively analysed all patients referring for CMR at Niguarda Hospital (Milan, Italy) from January 2006 to January 2015 for suspected CA. Primary outcome was all-cause mortality. We identified 42 patients and divided them into 2 groups, according to the presence (Group A) or absence (Group B) of a typical amyloidosis LGE pattern. At the end of the follow-up (median 37 months, interquartile range 10-50 months), 31 patients (74%) had died. The hazard ratio for all-cause death was 3.2 (95% confidence interval [CI] 1.5-6.4, p < 0.01) for Group A versus Group B. Median survival time was 17 months (95% CI 7-42 months) for Group A and 70 months (95% CI 49-94 months) for Group B (p < 0.01). Multivariate analysis did not find any adjunctive predictive role for biventricular volumes and ejection fraction, indexed left ventricular mass, transmitral E/e' at echocardiography, age at diagnosis or serum creatinine. CONCLUSION: In our population, a typical LGE pattern was significantly associated with higher mortality. Moreover, patients with a typical LGE pattern showed a globally worse prognosis. Our data suggest that the LGE pattern may play a central role in prognostic stratification of patients with suspected CA, thus prompting further diagnostic and therapeutic measures.

Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management.

BACKGROUND: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population. PATIENTS AND METHODS: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs. RESULTS: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001). CONCLUSIONS: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

Functional Improvement After Outpatient Cardiac Rehabilitation in Acute Coronary Syndrome Patients is Not Related to Improvement in Left Ventricular Ejection Fraction.

INTRODUCTION: Cardiac rehabilitation (CR) improves the functional capacity and the prognosis of patients with coronary artery disease. AIM: Our study was aimed at assessing the relationship between functional improvement (evaluated with 6-min Walk Test-6MWT) and the improvement in left ventricular ejection fraction (LVEF) after CR. METHODS: We collected data from 249 patients (age 66.79 ± 11.06 years; males 81.52%) with a recent history of Acute Coronary Syndrome that performed CR. The functional improvement after CR was expressed as the Δ between distance covered at the final versus the initial 6-min Walking Test (6-MWT), while LVEF was calculated with transthoracic echocardiogram at the beginning and at the end of the CR. RESULTS: Patients were divided accordingly to their pre-rehab LVEF (≥ 55% vs < 55%). With superimposable age and baseline 6MWT distance covered (434.58 vs 405.12 m, p = 0.08), the latter group presented higher Δ meter values at 6MWT (167.93 vs 193.97 m, p = 0.018). However, no statistically significant positive correlation between Δ meters and Δ LVEF was found. Moreover, linear regression analyses found that nor baseline LVEF nor Δ LVEF were significant determinants of Δ meters when considering the whole group, with age, basal 6MWT and peak CK-MB as additional covariates in the model. CONCLUSION: Although it could be expected that an increase in LVEF is related to the functional improvement after CR, no significant correlation was found in our population.

Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Codon 129 polymorphism of prion protein gene in sporadic Alzheimer's disease.

Codon 129 polymorphism of the prion protein gene represents a major genetic risk factor for Creutzfeldt-Jakob disease (CJD). Both CJD and Alzheimer's disease (AD) are brain amyloidoses and it would be possible that codon 129 polymorphism plays a role in the susceptibility to AD. In order to investigate this polymorphism in AD the distribution of polymorphic codon 129 of the PRNP gene in 194 probable AD and 124 controls selected in Italy and 109 neuropathologically verified AD and 58 matched controls recruited in the USA was studied. No significant association was found for the PRNP polymorphism in AD compared to controls either in Probable or in Definite AD series even after stratification for APOE polymorphism. This study does not support a role of PRNP polymorphism as a susceptibility factor for AD.

Changes in physical activity among coronary and hypertensive patients: A longitudinal study using the Health Action Process Approach.

OBJECTIVES: Physical activity (PA) is a key factor in cardiovascular disease prevention. Through the Health Action Process Approach (HAPA), the present study investigated the process of change in PA in coronary patients (CPs) and hypertensive patients (HPs). DESIGN: Longitudinal survey study with two follow-up assessments at 6 and 12 months on 188 CPs and 169 HPs. MAIN OUTCOME MEASURES: Intensity and frequency of PA. RESULTS: A multi-sample analysis indicated the equivalence of almost all the HAPA social cognitive patterns for both patient populations. A latent growth curve model showed strong interrelations among intercepts and slopes of PA, planning and maintenance self-efficacy, but change in planning was not associated with change in PA. Moreover, increase in PA was associated with the value of planning and maintenance self-efficacy reached at the last follow-up Conclusions: These findings shed light on mechanisms often neglected by the HAPA literature, suggesting reciprocal relationships between PA and its predictors that could define a plausible virtuous circle within the HAPA volitional phase. Moreover, the HAPA social cognitive patterns are essentially identical for patients who had a coronary event (i.e. CPs) and individuals who are at high risk for a coronary event (i.e. HPs).

Acute effect of high-fat meal on endothelial function in moderately dyslipidemic subjects.

OBJECTIVE: Hypercholesterolemia markedly impairs endothelial function. Whether this is the case for hypertriglyceridemia is less clear, however, and limited evidence exists on the effect of an acute increase in triglyceridemia caused by a high-fat meal. METHODS AND RESULTS: In 16 normotensive subjects with an untreated mild hypertriglyceridemia and dyslipidemia and in 7 normal controls, we measured radial artery diameter and blood flow by an echo-tracking device (NIUS02). Data were obtained at baseline, at the release of a 4-minute ischemia of the hand, which causes an increase in arterial diameter dependent on nitric oxide (NO) secretion, and at the release of a 12-minute exclusion of the arm by an arm cuff to obtain a larger increase in arterial diameter mainly of nonendothelial nature. Measurements were performed before and 6 hours after a high-fat meal (680 kcal/m(2) body surface; 82% lipids). In mild dyslipidemic hypertriglyceridemic subjects, the high-fat meal did not alter baseline blood pressure (beat-to-beat finger measurement), heart rate, radial artery diameter, and blood flow. It also did not alter the increase in blood flow induced by the 4-minute ischemia (+42.7+/-10.4 and +43.7+/-10.4 mL/min), whereas it markedly attenuated the concomitant increase in arterial diameter (+0.31+/-0.06 versus 0.13+/-0.06 mm; P<0.05). The alteration of the diameter response did not correlate with changes in total cholesterol, but it showed a significant correlation with the increase in serum triglycerides induced by high-fat meal (r=0.49, P<0.05). This attenuation was not seen in control subjects and in subjects in whom measurements were repeated after a 6-hour observation period. It was also not paralleled by an alteration of the endothelially independent response to a 12-minute ischemia whose larger effects on arterial diameter and blood flow were similar before and after the high-fat meal. CONCLUSIONS: Endothelial function is markedly impaired by a high-fat meal that causes an acute hypertriglyceridemia. This impairment is evident in dyslipidemic patients with baseline hypertriglyceridemia but not in normotriglyceridemic controls. An oral fat load was administered to 55 HIV-positive and 10 HIV-negative individuals. Postprandial clearance of triglyceride-rich lipoproteins was delayed in HIV-positive individuals. Compared with HIV-positive subjects not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial intermediate-density and low-density lipoproteins. Hypercholesterolemia impairs endothelial function, whereas the effect of hypertriglyceridemia is less clear. In normotensive subjects with an untreated hypertriglyceridemia and hypercholesterolemia, we measured endothelial function before and 6 hours after a high-fat meal. The results demonstrate that in moderately dyslipidemic patients, endothelial function is impaired by acute hypertriglyceridemia.

Alterations of cardiac structure in patients with isolated office, ambulatory, or home hypertension: Data from the general population (Pressione Arteriose Monitorate E Loro Associazioni [PAMELA] Study).

BACKGROUND: The prevalence and clinical significance of isolated office (or white coat) hypertension is controversial, and population data are limited. We studied the prevalence of this condition and its association with echocardiographic left ventricular mass in the general population of the PAMELA (Pressione Arteriose Monitorate E Loro Associazioni) Study. METHODS AND RESULTS: The study involved a large, randomized sample (n=3200) representative of the Monza (Milan) population, 25 to 74 years of age. Participants in the study (64% of the sample) underwent measurements of office, home, 24-hour ambulatory blood pressure, and echocardiography. Isolated office hypertension was defined as systolic or diastolic values >/=140 mm Hg or >/=90 mm Hg, respectively. Home and ambulatory normotension were defined according to criteria previously established from the PAMELA Study, for example, <132/83 mm Hg (systolic/diastolic) for home and 125/79 mm Hg for 24-hour average blood pressure. Treated hypertensive subjects were excluded from analysis that was made on a total of 1637 subjects. Depending on normotension being established on systolic or diastolic blood pressure measured at home or over 24 hours, the prevalence of isolated office hypertension ranged from 9% to 12%. In these subjects, left ventricular mass index was greater (P<0.01) than in subjects with normotension both in and outside the office. This was the case also for prevalence of left ventricular hypertrophy. Left ventricular mass index and hypertrophy were similarly greater in subjects found to have normal office but elevated home or ambulatory blood pressure ( approximately 10% of the population). CONCLUSIONS: Isolated office hypertension has a noticeable prevalence in the population and is accompanied by structural cardiac alterations, suggesting that it is not an entirely harmless phenomenon. This is the case also for the opposite condition, that is, normal office but elevated home or ambulatory blood pressure, which implies that limiting blood pressure measurements to office values may not suffice in identification of subjects at risk.

Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients.

OBJECTIVES: The present study was designed to assess whether a diuretic- or an angiotensin-converting enzyme inhibitor-based treatment can reduce arterial wall hypertrophy of a distal muscular medium-sized artery--the radial artery--and the stiffness of a proximal large elastic artery--the common carotid artery. BACKGROUND: Large-artery wall thickness and stiffness are increased during sustained essential hypertension and contribute to the increased risk of complications. Whether antihypertensive treatment can normalize the wall hypertrophy of conducting arteries has not yet been determined. METHODS: Seventy-seven elderly hypertensive patients were randomized to receive 9 months of double-blind treatment with perindopril (2 to 8 mg/day) or the diuretic combination of hydrochlorothiazide (12.5 to 50 mg/day) plus amiloride (1.25 to 5 mg/day) after a 1-month placebo washout period. If systolic blood pressure remained at >160 mm Hg after 5 months, chlorthalidone or atenolol was added, respectively. Arterial variables, including radial artery mass and common carotid artery compliance, were calculated from noninvasive measurements of internal diameter and wall thickness with the use of high resolution echo-tracking systems at baseline and after 5 and 9 months. RESULTS: During treatment, blood pressure and arterial variables changed to the same extent in both groups. After a 9-month treatment, systolic, diastolic and pulse pressures and radial artery wall thickness, mass and thickness/radius ratio decreased significantly (p < 0.01), whereas carotid compliance increased (p < 0.001). The decrease in radial artery thickness/radius ratio after a 9-month treatment was significantly related to the reduction in pulse pressure (p < 0.01), whereas the improvement in carotid compliance was related to the reduction in mean arterial pressure (p < 0.01). In healthy subjects and untreated hypertensive patients, radial artery diameter, wall thickness and thickness/radius ratio and carotid artery compliance did not change significantly during a 9-month observation period. CONCLUSIONS: These results indicate that in elderly hypertensive patients, both angiotensin-converting enzyme inhibitor- and diuretic combination-based treatments can reduce radial artery wall hypertrophy and improve carotid artery compliance.

Dante and cardiology: Physiopathology and clinical features of cardiovascular diseases in the Middle Ages.

Ancient non-medical texts can unexpectedly provide useful information on the development of knowledge about the heart and its diseases throughout history. The 750th anniversary of the birth of the Italian poet Dante Alighieri (1265-1321) provides a timely opportunity to analyze medical references in his works, in particular, focusing on literary descriptions that may be attributed to cardiovascular disorders. Dante's high level of medical knowledge, probably derived from his academic studies, is testified by his affiliation to the Florentine Guild of physicians and pharmacists. In all his works, the poet shows a deep interest for the heart. However, his anatomical and physiological knowledge of the circulatory system appears to be poor, probably due to it being based on theories and concepts brought forth by Aristotle and Galen, which were taught in medieval universities. Despite this, accurate descriptions of some symptoms (emotional syncope, orthopnea, dyspnea on exertion) and signs (ascites, paleness), which may be attributed to cardiovascular disorders, can be easily found in Dante's works, particularly in his masterpiece, the Divine Comedy. The literary and historical analysis of cardiovascular signs and symptoms allows us to assume that clinical features due to alterations of heart function were probably known by medieval physicians, but their etiology and pathophysiological mechanisms were not completely understood in that period. Historians of cardiology and clinicians should consider analysis of non-medical texts (including poetry) as an opportunity to better investigate the evolution of their discipline throughout the ages.

Sympathetic activation in the pathogenesis of hypertension and progression of organ damage.

Although animal models of hypertension have clearly shown that high blood pressure is associated with and is probably caused by an increase in sympathetic cardiovascular influences, a similar demonstration in humans has been more difficult to obtain for methodological reasons. There is now evidence, however, of increased sympathetic activity in essential hypertension. This article will review this evidence by examining data showing that plasma norepinephrine is increased in essential hypertension and that this is also the case for systemic and regional norepinephrine spillover, as well as for the sympathetic nerve firing rate in the skeletal muscle nerve district. Evidence will also be provided that sympathetic activation is a peculiar feature of essential hypertension, particularly in its early stages, with secondary forms of high blood pressure not usually characterized by an increased central sympathetic outflow. Humoral, metabolic, reflex, and central mechanisms are likely to be the factors responsible for the adrenergic activation characterizing hypertension, which may also promote the development and progression of the cardiac and vascular alterations that lead to hypertension-related morbidity and mortality, independent of blood pressure values. This represents the rationale for considering sympathetic deactivation one of the major goals of antihypertensive treatment.

Cardiopulmonary receptor modulation of plasma renin activity in normotensive and hypertensive subjects.

Cardiopulmonary receptors modulate renin release in several animals species. However, their involvement in reflex control of this humoral substance in humans is controversial. Furthermore, no information is available on the alteration of this control in hypertension. We studied the modulation of plasma renin activity (radioimmunoassay) in 12 normotensive subjects and in 12 age-matched subjects with untreated hypertension of mild or moderate degree. Cardiopulmonary receptors were stimulated by increasing central venous pressure (right atrial catheter) and cardiac volume (echocardiographic measurement) through passive leg raising and deactivated by reducing central venous pressure and cardiac volume through lower body negative pressure. The stimuli were maintained for 20 to 30 minutes, and their degree was set to avoid changes in blood pressure (indirect or direct measurements) and heart rate, thus avoiding involvement of arterial baroreceptors. In normotensive subjects, deactivation of cardiopulmonary receptors induced a progressive rise in plasma renin activity and stimulation of cardiopulmonary receptors induced a progressive fall. The reflex gain (ratio between plasma renin activity and central venous pressure or cardiac volume changes) was similar for deactivation and stimulation. During cardiopulmonary receptor deactivation, the gain corresponded to that obtained by dividing the increase in plasma renin by the reduction in central venous pressure induced by tilting. Cardiopulmonary receptor deactivation and stimulation also induced clear-cut changes in plasma renin activity in hypertensive subjects, but the percent magnitude of the reflex plasma renin activity excursion was less than that in normotensive subjects. These observations indicate that cardiopulmonary receptors modulate plasma renin activity in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary reflex before and after regression of left ventricular hypertrophy in essential hypertension.

Studies that have examined the cardiopulmonary receptor control of circulation in hypertension have produced conflicting results. In 10 normotensive subjects and in age-matched essential hypertensive subjects without (n = 10) or with left ventricular hypertrophy (n = 12), as well as in seven subjects of the latter group restudied after 1 year of treatment that induced regression of cardiac hypertrophy, we examined the cardiopulmonary reflex by increasing central venous pressure and stimulating cardiopulmonary receptors through passive leg raising and by reducing central venous pressure and deactivating cardiopulmonary receptors through nonhypotensive lower body negative pressure. Reflex responses were measured as changes in forearm vascular resistance (mean blood pressure divided by plethysmographically measured blood flow), plasma norepinephrine concentration, and plasma renin activity. In hypertensive subjects without left ventricular hypertrophy, stimulation and deactivation of cardiopulmonary receptors caused changes in forearm vascular resistance, norepinephrine concentration, and plasma renin activity that were modestly reduced as compared with those in normotensive subjects. However, all these changes were markedly reduced in hypertensive subjects with left ventricular hypertrophy. Following regression of left ventricular hypertrophy, the changes in vascular resistance, plasma norepinephrine, and plasma renin activity induced by cardiopulmonary receptor manipulation all improved markedly. These results demonstrate that cardiopulmonary receptor regulation of peripheral vascular resistance and of neurohumoral variables is impaired in essential hypertension and that the impairment is much more pronounced when this condition is associated with cardiac structural alterations. Therapeutic regression of these alterations, however, leads to a marked improvement of this reflex, with consequent favorable effects on circulatory homeostasis.

Effect of sympathectomy on mechanical properties of common carotid and femoral arteries.

Sympathetic stimulation is accompanied by a reduction of arterial distensibility, but whether and to what extent elastic and muscle-type arterial mechanics is under tonic sympathetic restraint is not known. We addressed this issue by measuring, in the anesthetized rat, the diameters of the common carotid and femoral arteries with an echo-Doppler device (NIUS 01). Blood pressure was measured by a catheter inserted contralaterally and symmetrically to the vessel where the diameter was measured. Arterial distensibility over the systolic-diastolic pressure range was calculated according to the Langewouters formula. Data were collected in 10 intact (vehicle pretreatment) and 9 sympathectomized (6-hydroxydopamine pretreatment) 3-month-old Wistar-Kyoto rats. Compared with the intact animals, sympathectomized rats showed a marked increase in arterial distensibility over the entire systolic-diastolic pressure range. When quantified by the area under the distensibility-pressure curve, the increase was 59% and 62% for the common carotid and femoral arteries, respectively (P<.01 for both). In the femoral but not in the common carotid artery, sympathectomy was accompanied also by an increase in arterial diameter (+18%, P<.05 versus intact). Therefore, in the anesthetized normotensive rat, sympathetic activity exerts a tonic restraint on large-artery distensibility. This restraint is pronounced in elastic vessels and even more pronounced in muscle-type vessels.

Heart rate-dependent stiffening of large arteries in intact and sympathectomized rats.

In the anesthetized rat, acute increases in heart rate are accompanied by a reduction in arterial distensibility, which is a significant phenomenon in elastic-type vessels such as the common carotid but much less evident in muscle-type vessels such as the femoral artery. Because the sympathetic nervous system importantly reduces arterial distensibility, the present study aimed to determine whether sympathetic influences (1) are involved in the heart rate-dependent changes in arterial distensibility and (2) exert differential effects on elastic-type versus muscle-type arteries. To address this issue, 9 sympathectomized (6-hydroxydopamine) and 10 vehicle-treated, 12-week-old, pentobarbitone-anesthetized Wistar-Kyoto rats were subjected to atrial pacing via a transjugular catheter at 5 different randomly sequenced rates (280, 310, 340, 370, and 400 bpm). After each step, spontaneous sinus rhythm was allowed to return to normal. Common carotid and femoral artery diameters were measured by an echo Doppler device (NIUS 01), and blood pressure was measured via catheter inserted into the contralateral vessel. Arterial distensibility was calculated over the systolic-diastolic pressure range according to the Langewouters formula. In the common carotid artery, progressive increases in heart rate determined progressive and marked reductions of distensibility (range, 15% to 43%) in sympathectomized and intact rats. In the femoral artery, the stiffening effect of tachycardia was present in sympathectomized rats (range, 21% to 42%), at variance with the inconsistent changes observed in intact rats. In conclusion, our experiments support the notions (1) that in predominantly elastic-type arteries, the stiffening effect of tachycardia is exerted independently of sympathetic modulation of the vessel wall properties and (2) that in predominantly muscle-type arteries, removal of sympathetic influences unmasks the stiffening effect of tachycardia.

Effects of prolonged immobilization of the limb on radial artery mechanical properties.

Physical training is associated with an increase in arterial distensibility. Whether the effect of training on this variable is evident also for ordinary levels of exercise or no exercise is unknown, however. We have addressed this issue by investigating the effect on radial artery distensibility of prolonged monolateral immobilization of the ipsilateral limb versus the following resumption of normal mobility. We studied 7 normotensive subjects (age, 25.4+/-3.0 years; systolic/diastolic blood pressure, 119+/-9/68+/-6 mm Hg, mean+/-SE) in whom 1 limb had been immobilized for 30 days in plaster because of a fracture of the elbow. At both the day after plaster removal and after 45 days of rehabilitation, radial artery distensibility was evaluated by an echo-tracking device (NIUS-02), which allows arterial diameter to be measured noninvasively and continuously over all pressures from diastole to systole (finger monitoring), with the distensibility values being continuously derived from the Langewouters formula. In both instances, the contralateral arm was used as control. Immediately after removal of the plaster, radial artery distensibility was markedly less in the previously immobilized and fractured limb compared with the contralateral limb (0.4+/-0.1 versus 0.8+/-0.1, 1/mm Hg 10(-3), P<0.05). After rehabilitation, the distensibility of the radial artery was markedly increased in the previously fractured limb (0.65+/-0.1 1/mm Hg 10(-3), P<0.05), whereas no change was seen in the contralateral limb. Thus, complete interruption of physical activity is associated with a marked reduction of arterial distensibility, indicating that even an ordinary level of activity plays a major role in modulation of arterial mechanical properties.

Reflex vasopressin and renin modulation by cardiac receptors in humans.

Animal studies have shown that vasopressin secretion is modulated by arterial baroreceptors and cardiopulmonary volume receptors. Whether this is the case also in humans is controversial, however. To determine whether vasopressin is reflexly modulated by cardiac volume receptors, we studied the effect on plasma vasopressin (venous blood, radioimmunoassay) of reducing venous return and left ventricular end-diastolic diameter (echocardiography) by producing a 20-minute lower body negative pressure in 14 healthy subjects (aged 49.3 +/- 3.8 years, mean +/- SEM). The data were compared with those of 14 age-matched heart-transplant recipients, i.e., subjects with cardiac denervation. In healthy subjects, lower body negative pressure at -15 mm Hg caused a modest reduction in left ventricular end-diastolic diameter (-5 +/- 3.4%) and no change in vasopressin, whereas lower body negative pressure at -37.5 mm Hg caused a more marked reduction in left ventricular end-diastolic diameter (-12 +/- 2.5%) and a small, variable, but overall statistically significant (p < 0.05) increase in vasopressin (+145 +/- 46%, p < 0.01). The left ventricular end-diastolic diameter changes induced by the two lower body negative pressure stimuli were similar in heart-transplant recipients, but the vasopressin increase seen with the lower body negative pressure at -37.5 mm Hg was abolished. The marked increase in plasma renin activity and forearm vascular resistance induced by lower body negative pressure in healthy subjects was also abolished or drastically attenuated in heart-transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-converting enzyme inhibition and radial artery compliance in patients with congestive heart failure.

Congestive heart failure is characterized by a clear-cut impairment of arterial compliance of medium-sized arteries, but whether this alteration is irreversible or can be favorably affected by cardiovascular drugs currently used in congestive heart failure treatment is unknown. We studied 9 congestive heart failure patients (New York Heart Association class II; age, [mean +/- SEM] 60.7 +/- 3.3 years) receiving diuretic and digitalis treatment in whom arterial compliance was assessed at the level of the radial artery by an echotracking device capable of measuring the arterial diameter along the entire cardiac cycle. Beat-to-beat arterial blood pressure was concomitantly measured by a Finapres device that allowed diameter-pressure curves and compliance-pressure curves (Langewouters' formula) to be calculated for the entire systolic-diastolic blood pressure range. Arterial compliance was expressed as the area under the compliance-pressure curve normalized for pulse pressure (compliance index). Data were collected before and after 4 and 8 weeks of oral administration of benazepril (10 mg/day). Ten healthy subjects were studied before and after an observational period of 4 weeks (5 subjects) or 8 weeks (5 subjects), and 9 age-matched mildly essential hypertensive subjects studied before and after 4 to 12 weeks of benazepril administration served as control subjects. In congestive heart failure patients, baseline compliance index was significantly less than in normotensive and hypertensive subjects. However, the compliance index showed a marked increase after 4 weeks of benazepril administration (+95.7 +/- 24.9%, P < .05); the increase was also marked after 8 weeks of angiotensin-converting enzyme inhibitor treatment (+77.7 +/- 4.2%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)