Effect of Domperidone on the Bromocriptine-Induced Antihypertensive Action in Hypertensive Patients

Dopaminergic receptors have been involved in the cardiovascular and renin-angiotensin systems (RAS). We have recently reported that bromocriptine is an effective antihypertensive drug by stimulating DA(2) dopaminergic receptors. However, the nature of the dopaminergic receptors in RAS has not been established. Ten outpatients with essential hypertension were treated at the Vargas Hospital with bromocriptine (BR) (11.25 mg day(minus sign1)), a DA(2) dopaminergic agonist, for a 2-week period, after which an oral dose of 30 mg day(minus sign1) of domperidone (DO), a peripheric DA(2) dopaminergic antagonist, was added for 2 additional weeks. The active period was preceeded by a 2-week placebo period. Bromocriptine decreased blood pressure (BP) significantly by 19/9 mm Hg (systolic/diastolic BP). Bromocriptine did not cause heart rate (HR) changes. Bromocriptine decreased plasma aldosterone (ALD) without altering plasma renin activity (PRA). Domperidone partially blocked bromocriptine-induced antihypertensive submaximal treadmill effects and reversed ALD decrease. Exercise response was not significantly altered by BR + DO. We conclude the following: (1) BR is an effective antihypertensive agent; (2) BR seems to be acting at both the central and peripheric nervous systems, and (3) the nature of the dopaminergic receptor involved in renin secretion does not seem to be DA(2).     

Heart rate and blood pressure variability in subjects with vasovagal syncope

Autonomic nervous system control in subjects with vasovagal syncope is controversial. In the present study, we used short-term spectral analysis to evaluate autonomic control in subjects with recurrent vasovagal syncope. We assessed the ability of spectral indices of HR (heart rate) variability to predict tilt-test responses. A series of 47 outpatients with recurrent vasovagal syncope and with positive responses to head-up tilt testing underwent a further study of RR variability during controlled breathing at rest and during tilt testing. During controlled breathing, RR interval variability of total power (TP(RR); P<0.001), low-frequency power (LF(RR); P<0.05), high-frequency power (HF(RR); P<0.001) and HF expressed in normalized units (HFnu(RR); P<0.001) were all higher, and LF expressed in normalized units (LFnu(RR)) and LF/HF ratio were lower in subjects with vasovagal syncope than in controls (P<0.001). To assess the ability of spectral components of RR variability to predict tilt-test responses, we prospectively studied 109 subjects with recurrent vasovagal syncope. The two normalized measures, HFnu(RR) and LFnu(RR), determined during controlled breathing alone predicted a positive tilt-test response (sensitivity, 76%; specificity, 99%; positive predictive value, 96%; and negative predictive value, 90%). During tilting, subjects with vasovagal syncope had lower SBP (systolic blood pressure; P<0.05), LF component of peak SBP variability (LF(SBP)) and LFnu(RR) than controls, and higher TP(RR), HF(RR), HFnu(RR) and alpha HF (P<0.001). These spectral data indicate that vagal sinus modulation is increased at rest in subjects with vasovagal syncope. Spectral analysis of RR variability during controlled breathing, a procedure that predicts tilt-test responses, could be a useful guide in choosing the method of tilt testing.     

Effects of sildenafil citrate (viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure

Background Cases of sudden death associated with sildenafil citrate use have been reported in men with coronary artery disease. The aim of this study was to investigate the drug's effect on cardiac repolarization and sinus autonomic and vascular control in men with mild chronic heart failure (CHF; New York Heart Association classification II). Changes in these variables could predispose patients to malignant ventricular arrhythmias. Method We measured QT dispersion, the QT-RR slope, and the index of QT variability (QTVI) and analyzed spectral power of RR and systolic blood pressure variability in 10 men with dilated cardiomyopathy and in 10 control subjects after administration of a single 50-mg oral dose of sildenafil citrate or placebo at rest (not followed with any attempt at intercourse). Results In both groups, oral sildenafil citrate decreased the systolic blood pressure (P <.05) and increased the heart rate (P <.05). In subjects with CHF, it also increased the QT-RR (P <.001) and QTVI (from −0.45 ± 0.07 to −0.27 ± 0.07; P <.001), but in controls, it increased the QTVI (from −1.20 ± 0.08 to −0.78 ± .014; P < .001). In these subjects and controls, oral sildenafil citrate induced a significant reduction in high frequency, expressed in absolute power (subjects with CHF: from 4.04 ± 0.14 to 3.43 ± 0.16 natural logarithm ms²; P <.001; controls: from 5.61 ± 0.44 to 4.98 ± 0.32 natural logarithm ms²; P <.05) and in normalized units (P <.05). In subjects with CHF but not in controls, it also significantly increased the low frequency to high frequency ratio (from 1.3 ± 0.12 to 1.89 ± 0.16; P <.001) and low frequency expressed in normalized units (P <.05).Sildenafil citrate caused no significant changes in the QT interval or dispersion. Conclusion These findings indicate that, in men with heart failure, sildenafil citrate reduces vagal modulation and increases sympathetic modulation, probably through its reflex vasodilatory action. The autonomic system changes induced with sildenafil citrate could alter QT dynamics. Both changes could favor the onset of lethal ventricular arrhythmias. At the dose usually taken for erectile dysfunction, sildenafil citrate has no direct effect on cardiac repolarization (QT interval or dispersion). (Am Heart J 2002;143:703-10.)     

Immunophenotyping and T-cell proliferative capacity in a healthy aged population

The age-related decline of immunological functions is well established but it remains largely unknown which specific changes are related to disease. We analyzed peripheral blood lymphocytes of 42 healthy elderly as well as 24 healthy young subjects from southern Brazil. No differences in phytohemagglutinin-induced proliferation and CD4:CD8 ratio were found between the subjects. However, CD4 expression (considering mean fluorescence intensity) was found up regulated in elderly subjects. No changes in activation molecules CD25, CD28, CD69 and CD95 were observed. A reduced proportion of naive (CD45RA+) T cells was found in the elderly compared to young subjects. No changes in adhesion molecule expression (CD11c and CD31) were observed. However, the frequencies of CD49d-positive cells, as well as expression of CD62L, were increased in the eldery subjects. We further described two subgroups of eldery subjects with an immunological risk profile defined by lower CD4:CD8 ratio and reduced proliferative response to mitogens. These data suggest that healthy aging is associated with intact T-cell proliferation and some compensatory immunophenotypical changes. This revised version was published online in July 2006 with corrections to the Cover Date.     

Patients with cardiac disease: Changes observed through last decade in out-patient clinics

AIM: To describe current profile of patients with cardio-vascular disease(CVD) and assessing changes through last decade.METHODS: Comparison of patients with established CVD from two similar cross-sectional registries performed in 1999(n = 6194) and 2009(n = 4639).The types of CVD were coronary heart disease(CHD),heart failure(HF) and atrial fibrillation(AF).Patients were collected from outpatient clinics.Investigators were 80% cardiologist and 20% primary care practitioners.Clinical antecedents,major diagnosis,blood test results and medical treatments were collected from all patients.RESULTS: An increase in all risk factors,except for smoking,was observed;a 54.4% relative increase in BP control was noted.CHD was the most prevalent CVD but HF and AF increased significantly,41.5% and 33.7%,respectively.A significant reduction in serum lipid levels was observed.The use of statins increased by 141.1% as did all cardiovascular treatments.Moreover,the use of angiotensin-renin system inhibitors in patients with HF,beta-blockers in CHD patients or oral anticoagulants in AF patients increased by 83.0%,80.3% and 156.0%,respectively(P < 0.01).CONCLUSION: The prevalence of all cardiovascular risk factors has increased in patients with CVD through last decade.HF and AF have experienced the largest increases.     

Benign positional vertigo: prognostic factors.

OBJECTIVE/HYPOTHESIS: We sought to assess prognostic factors associated with initial successful treatment and recurrence of benign paroxysmal positional vertigo (BPPV) with the canalith repositioning (CRP) maneuver with mastoid vibration. STUDY DESIGN AND SETTING: We conducted a retrospective chart review of 104 consecutive BPPV patients at a tertiary care referral center during 1999. METHODS: The main outcome measures were resolution of BPPV and absence of nystagmus on Hallpike maneuver. RESULTS: Ninety-three patients (89.4%) experienced initial symptom resolution, and 21 of the initially successful patients had a recurrence (recurrence rate of 22.6%). Prior trauma or labyrinthitis was found to predict the lowest initial CRP success. Endolymphatic hydrops and central nervous system-related dizziness as cofactors with BPPV were associated with the highest recurrence rates. CONCLUSION AND SIGNIFICANCE: Specific concurrent otologic conditions are associated with different outcomes in BPPV.