Are 5-HT1A receptors involved in the control of reflex bradycardia induced by intracoronary injection of contrast medium in humans?

Transient vagal bradycardia occurring during coronary arteriography (CA) immediately following intracoronary injection of ionic contrast medium is believed to be a component of the von Bezold-Jarisch reflex (BJ). Data obtained from experimental animals using buspirone (BSP) and other 5-HT1A receptor ligands suggest that these serotonergic receptors modulate the excitability of cardiac vagal motoneurones (CVM). This is a preliminary investigation of the possible effects of BSP in altering the bradycardia of patients submitted to CA for diagnostic purposes. Patients were divided into two age- and race-matched groups: control (C:N = 45, age 58.6 +/- 1.6 years, mean arterial blood pressure (MAP) 109 +/- 2.4 mmHg, heart rate (HR) 79 +/- 2.9 bpm) and BSP-treated (B:N = 14, age 58.9 +/- 2.1 years, MAP 111 +/- 4.5 mmHg, HR 76 +/- 3.4 bpm). The prevalent underlying pathology was coronary artery disease. Patients with acute angina, congestive heart failure, symptomatic arrhythmia and patients requiring atropine were excluded. CA was performed by a standard procedure using diatrizoate (MD-76) as contrast agent. The left and then the right coronary ostia were selectively catheterized and 8 ml of contrast medium was injected (over a period of 3 sec). HR was measured from ECG tracings before and after contrast injection into the left (LC) and right (RC) coronary arteries. Peak bradycardia was measured as the longest R-R interval during the first 15 sec after the injection minus the pre-injection R-R value, and reported as delta R-R. Group B patients received BSP tablets 48 and 24 h before the examination (30 mg/day po). There was no statistically significant difference (P > 0.05) in bradycardia between groups (C:LC = -147 +/- 23, RC = -155 +/- 25; B: LC = -143 +/- 44, RC = -234 +/- 56 msec). These results suggest that, in contrast to experimental animals, the central 5-HT1A receptors of humans are not relevant for modulating the excitability of CVM in the BJ reflex. However, since drugs and diseases can affect the responses, further studies are necessary to clarify this issue.

[Captopril in the treatment of patients with congestive heart failure. Its bicycle ergometry evaluation]. / Captopril no tratamento de pacientes com insuficiência cardíaca congestiva. Avaliação cicloergométrica.

PURPOSE: To analyze the physical performance of the patients with congestive heart failure (CHF), grades I and II of the New York Heart Association (NYHA), submitted to ergometric test: 1) under conventional treatment with digitalis and diuretic; 2) with an angiotensin converting enzyme inhibitor, captopril, associate with conventional treatment; 3) using captopril associated with digitalis or diuretic. METHODS: A randomized double blind study was performed in 20 patients with CHF (I and II-NYHA) submitted to ergometric test in different therapeutic phases. The initial workload was 5 watts and load was increased until the appearance of limiting symptoms. RESULTS: The introduction of captopril to the conventional treatment for CHF or associated with digitalis or diuretic promotes significant increase in the duration of the physical exercise, in the oxygen consumption and in the total workload during the ergometric test. CONCLUSION: In the initial forms of CHF, captopril provides better physical performance when compared with conventional treatment and the diuretic treatment can be changed for the angiotensin converting enzyme inhibitor with equal efficacy.

[Treatment of mild and moderate cardiac failure with captopril. A multicenter study]. / Tratamento da insuficiência cardíaca leve e moderada com captopril. Estudo multicêntrico.

PURPOSE: Evaluation of the clinical effects of captopril addition to the conventional therapy of functional class II and III (NYHA) congestive heart failure (CHF). METHODS: One hundred and fifteen patients with CHF, 46 (40%) class II and 69 (60%) class III, on conventional treatment (digitalis and diuretic) were the subject of this study. The age ranged from 22 to 75 years (mean 56.6 +/- 11); 67 were male and 66 were caucasians. The etiologies of the heart failure were: hypertensive heart disease 47 (40.9%), ischemic heart disease 27 (23.5%), Chagas cardiomyopathy 20 (17.4%), idiopathic cardiomyopathy 15 (13.0%), and other causes 6 (5.2%). Diuretic and digitalis were maintained in the same dosage during all the treatment. Captopril therapy was started with 6.25 mg b.i.d. or t.i.d., and the dosage was increased gradually to 25 mg b.i.d. or t.i.d. The duration of the study was 12 weeks. Clinical visits occurred every four weeks and laboratory tests were performed in the beginning and at the end of the study. RESULTS: The dosage of captopril ranged from 12.5 to 75 mg (mean 28.5 +/- 13.1 mg/day). The addition of captopril to the conventional therapy of CHF was associated with significant reduction (p < 0.01) of heart rate, systolic and diastolic blood pressure. In the end of the study 13 patients (11.3%) were in functional class III, 50 (43.5%) in class II and 52 (45.2%) in class I. Globally, functional class was improved in 98 (85.2%) patients and remained unchanged in 17 (14.8%) (p < 0.01). The side effects (dizziness, cough, hypotension and headache) were moderate and uncommon and did not need interruption of the treatment. CONCLUSION: The addition of captopril to the conventional therapy of class II and III CHF was associated with significant improvement of functional class and with good tolerability.

Eficácia e segurança do captopril em baixas doses, isolado ou associado a diuréticos, no tratamento da hipertens leve e moderada / Efficacy and safety of low doses of captopril, alone or associated with diuretics, in the treatment of mild and moderate hypertension

Trinta e tres pacientes com hipertensao arterial leve e moderada foram tratados com captopril em baixas doses (50 a 75 mg/ dia), isoladamente ou associado a diuretico, durante 10 semanas. O captopril isoladamente normalizou a pressao arterial (pressao diastolica 95 mmHg) em 11 (33,3%) pacientes. Em 19 (57,5%) pacientes, a adicao de diureticos proporcionou a normalizacao dos niveis tensioanis. Tres (9,2%) pacientes nao obtiveram resposta satisfatoria ao tratamento. Nao foram observadas alteracoes significativas nos exames laboratoriais realizados, assim como os efeitos adversos relatados foram irrelevantes, com excessao de um paciente que apresentou reacao urticariforme sendo necessario suspender a medicacao.Estes dados sugerem que o captopril, em baixas doses, isolado ou associado a diureticos, constitui uma opcao eficaz e segura no tratamento da hipertensao leve e moderada

Are 5-HT1A receptors involved in the control of reflex bradycardia induced by intracoronary injection of contrast medium in humans?

Transient vagal bradycardia occuring during coronary arteriography (CA) immediately following intracoronary injection of ionic contrast medium is believed to be a component of the von Bezold-Jarisch reflex (BJ). Data obtained from experimental animals using buspirone (BSP) and other 5-HT1A receptor ligands suggest that these serotonergic receptors modulate the excitability of cardiac vagal motoneurones (CVM). This is a preliminary investigation of the possible effects of BSP in altering the bradycardia of patients submitted to CA for diagnostic purpose. Patients were divided into two age-and racematched groups: control (C:N=45, age 58.6 + 1.6 years, mean arterial blood pressure (MAP) 109 + 2.4 mmHg, heart rate (HR) 79 + 2.9 bpm) and BSP-treated (B:N=14, age 58.9 + 2.1 years, MAP 111 + 4.5 mmHg, HR 76 + 3.4 bpm). The prevalent underlying pathology was coronary artery disease. Patients with acute angina, congestive heart failure, symptomatic arrhythmia and patients requiring atropine were excluded. CA was performed by a standard procedure using diatrizoate (MD-76() as contrast agent. The left and then the right coronary ostia were selectively catheterized and 8 ml of contrast medium was injected (over a period of 3 sec). HR was measured from ECG tracing before and after contrast injection into the left (LC) and right (RC) coronary arteries. Peak bradycardia was measured as the longest R-R interval during the first 15 sec after the injection minus the pre-injection R-R value, and reported as deltaR-R. Group B patients received BSP tablets 48 and 24 h before the examination (30 mg/day po). There was no statistically significant difference (P>0.05) in bradycardia between groups (C:LC=-147 + 23,RC=-155+25; B:LC=-143 + 44,RC=-234 + 56 msec). These results suggest that, in contrast to experimental animals, the central 5-HT1A receptors of humans are not relevant for modulating the excitability of CVM in the BJ reflex. However, since drugs and diseases can affect the responses, further studies are necessary to clarify this issue.