Intrinsic Adaptation of SHR Right Atrium Reduces Heart Rate.

Hypertension represents an autonomic dysfunction, characterized by increased sympathetic and decreased parasympathetic cardiovascular tone leading to resting tachycardia. Therefore, studies assessing hypertension-associated changes in isolated cardiac tissues were conducted under electric field stimulation to stimulate the neurons. Herein, we characterize the influence of the autonomic neurotransmitter on the baseline atrial chronotropism of unpaced isolated right atria of normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). Our results revealed a resting bradycardia in tissues from SHR in comparison to NWR. The release of autonomic neurotransmitters, acetylcholine or norepinephrine, still occurs in the electrically unstimulated right atrium, after excision of the sympathetic nerve, which could explain differences in basal heart rate between NWR and SHR. Nicotine and the acetylcholinesterase inhibitor physostigmine reduced the chronotropism of right atria from either NWR or SHR. Conversely, the muscarinic receptor antagonist atropine did not affect the basal chronotropism of tissues from both strains. Furthermore, tyramine increased the chronotropism of NWR and SHR atria indicating availability of the neuronal stocks of noradrenaline. Although the monoamine uptake inhibitor cocaine increased right atrium chronotropism in both strains, the basal heart rate was not affected by the ß-adrenoceptor antagonist propranolol. In summary, after acute section of the sympathetic nerve, autonomic neurotransmitters are still released either in resting conditions or upon pharmacological stimulation of right atria from both strains. Nevertheless, autonomic neurotransmission does not affect resting chronotropism, nor is the responsible for reduced basal heart rate of the isolated right atrium of hypertensive rats.

Acute effect of iloprost inhalation on right atrial function and ventricular dyssynchrony in patients with pulmonary artery hypertension.

BACKGROUND: Right atrium function and ventricular function have significant prognostic value in pulmonary arterial hypertension patients. Acute changes in right ventricular synchrony and right atrium function postiloprost inhalation have not been evaluated. METHODS: Cross-sectional study. Consecutive pulmonary arterial hypertension patients (group I from Nice classification) were included. Echocardiographic right atrium and right ventricular function pre- and postiloprost inhalation, including a right ventricular dyssynchrony index and right atrium function using speckle tracking, were performed in all patients. RESULTS: Twenty pulmonary arterial hypertension patients, 44±7 years and 90% females, were included. After iloprost inhalation, we observed a significant increment in right ventricular fractional area change and a significant decrease in right ventricular dyssynchrony index (21.4±5.6% vs 26.1±4.0 %, P=.007 and 79±44 vs 32±22 mseconds, P<.01, respectively), also an improvement in right atrium reservoir function (8.6±3.1% vs 11.7±3.5 %, P=.002). CONCLUSIONS: Iloprost inhalation induces acute changes in right ventricular function, dyssynchrony, and right atrium performance that may add relevant clinical information in the management and risk stratification of pulmonary arterial hypertension patients.

Cambios agudos en la función auricular derecha post uso de iloprost inhalatorio en pacientes con hipertensión arterial pulmonar: estudio con técnicas de deformación de imagen / Acute changes in right atrial funcion after Iloprost inhalation in patients with pulmonary hypertension: a study using image deformation techniques

Introducción: El efecto de prostanoides inhalatorios sobre la función auricular derecha (AD) en hipertensión arterial idiopática (HAP) no ha sido estudiado. Objetivo: Evaluar cambios agudos en la función AD y función diastólica del ventrículo derecho en pacientes con HAP post uso de Iloprost inhalatorio. Métodos: Se incluyeron pacientes con HAP sin uso previo de prostanoides. Se realizó un ecocardiograma transtorácico basal y 30 min posterior a la inhalación de iloprost. Se midió dimensión AD, relación E/e' y strain de la AD por speckle tracking, registrando la onda negativa de contracción auricular (SaAD) y la onda positiva de la fase de reservorio (SsAD). Se midió el tiempo de inicio de la fase de reservorio AD durante el sístole ventricular. Resultados: Se estudiaron 16 pacientes (15 mujeres), con edad promedio 44 ± 7,8 años. Post Iloprost disminuyó el volumen AD (basal: 140ml, post Iloprost: 109 ml; p 0,008) y las presiones de llenado (E/e’ basal: 13, post Iloprost: 9,8; p 0,028). No se registraron diferencias en el SaAD (basal: -8,4%, post Iloprost: -8,5%; p 0,834). El SsAD fue mayor post Iloprost (basal: 8,6%, post Iloprost: 11,7%; p 0,002) iniciándose antes durante el sístole ventricular (basal: 445ms, post Iloprost: 368ms; p 0,001). Conclusión: Con Iloprost inhalatorio en pacientes con HAP se observa una reducción aguda en el tamaño de la AD y en las presiones de llenado del VD. La deformación durante la fase de reservorio de la AD aumenta y se inicia significativamente antes. Esto sugiere que el Iloprost podría mejorar en forma aguda el trabajo mecánico de la AD en paciente con HAP.

Background: The effects of inhaled prostanoids on right atrial (RA) function in patients with Pulmonary Arterial Hypertension (PAH) have not been studied. We evaluated acute changes in RA function and right ventricular diastolic function after inhaled iloprost. Methods: We included PAH patients without prior prostanoid treatment. A surface echocardiogram was performed at baseline and 30 minutes after iloprost inhalation. Measurements included RA dimensions, right E/e’ ratio and RA strain by speckle tracking, registering a RA contraction wave (RASa) and RA reservoir wave (RASs). RA time to peak of deformation during the reservoir phase was also measured. Results: We included 16 patients (15 females, aged 44±7.8 years. Post iloprost there was a reduction in RA volume (baseline: 140ml, post iloprost: 109ml; p 0.008) and right ventricular filling pressure (baseline E/e’: 13, post iloprost: 9.8; p 0.028). There was no difference in the magnitude of the RASa wave (baseline: -8.4%, post iloprost: -8.5%; p 0.834). The RASs wave was larger post iloprost (baseline: 8.6%, post iloprost: 11.7%; p 0.002), and began earlier (baseline RA time to peak of deformation during reservoir phase: 445ms, post iloprost: 368ms; p 0.001). Conclusion: Inhaled iloprost acutely reduces RA size and right ventricular filling pressure in patients with HAP It also significantly increases the magnitude of RA systolic deformation as well as making it occur earlier in RA filling phase. This suggests that iloprost might improve RA mechanical performance.

An evaluation of the cardiotoxicity of imatinib mesylate.

We studied 103 consecutive patients with chronic myeloid leukaemia on treatment with imatinib (IM) and 57 patients with chronic myeloproliferative disorders not treated with IM in order to evaluate its cardiotoxicity. There was no statistical difference regarding cardiac symptoms and signs, BNP levels and echocardiographic measurements for IM and control groups, except for peripheral oedema, more frequent in the IM group. Four patients in the IM group presented a BNP level >100pg/ml, one of them with depressed LVEF. IM was not related to systematic deterioration of cardiac function, but there is still a possibility of isolated cases of cardiotoxicity.

Acute hemodynamic effects of pulsed delivery of low flow nasal nitric oxide in children with pulmonary hypertension.

We studied 8 children, ages 8 months to 14 years, during cardiac catheterization in order to determine the acute hemodynamic effects of pulsed nasal cannula delivery of nitric oxide (NO) in children with pulmonary hypertension. NO was administered by continuous mask or pulsed nasal cannula in random order. All patients effectively triggered the NO pulsing device. Pulsed delivery of inhaled NO lowered mean pulmonary artery pressure and pulmonary vascular resistance as effectively as mask delivery of NO. Pulsed inhaled NO delivery may potentially be useful for the long-term domiciliary treatment of pulmonary hypertension in children.

Comparison of isoflurane, halothane and fentanyl in patients with decreased ejection fraction undergoing coronary surgery.

The aim of the study was to compare three anaesthetic agents in patients with ejection fraction below 0.40 subjected to coronary revascularization surgery. Twenty five elective coronary surgical patients with ejection fraction below 0.40 were prospectively studied. Premedication was pethidine 1 mg/kg and induction was fentanyl 0.03 mg/kg and pancuronium 0.1 mg/kg. The patients were randomized to one of three maintenance techniques (fentanyl, isoflurane or halothane). Radial arterial pressure, heart rate, right atrial pressure, pulmonary arterial and occluded pressures, and thermodilution cardiac output were measured, and cardiac index and resistance calculated, at the following times: before induction; 5 min after intubation; 2 min after sternotomy; immediately after discontinuation of bypass; 15 min afterwards; immediately after sternal closure; during suture of the skin; 5 min after arrival in the postoperative care unit; and 60 min postoperatively. Mean arterial pressure decreased significantly in the isoflurane group and nonsignificantly in the halothane group after induction. Cardiac index decreased significantly in the isoflurane group and nonsignificantly in the halothane group after induction and after sternotomy. Neither pressure nor flow decreased in patients receiving fentanyl. Following weaning from cardiopulmonary bypass, systemic vascular resistance decreased significantly in all groups. Cardiac index, however, did not increase above control values and arterial pressure consequently decreased; there was no significant difference between groups.

Low doses of inhaled nitric oxide in heart transplant recipients.

BACKGROUND: The purpose of this study was to assess the hemodynamic effects of low doses of inhaled nitric oxide in patients after orthotopic heart transplantation. METHODS: Two hours after the operation 10 adult patients who were still under anesthetic effects and undergoing mechanical ventilation inhaled, during 60 minutes, a mixture of nitrogen, oxygen, and nitric oxide (20 ppm). A standard profile of hemodynamic data was collected at baseline, at 30 minutes, at 30 more minutes of inhalation, and at the same points after nitric oxide suspension. RESULTS: A significant decrease was found from baseline to 60 minutes, immediately after nitric oxide inhalation in the following: systemic vascular resistance index 1268 +/- 409 to 1090 +/- 354 (p = 0.0161); pulmonary vascular resistance index 252 +/- 124 to 154 +/- 98 (p < 0.05); pulmonary vascular resistance index/systemic vascular resistance index ratio 0.21 +/- 0.09 to 0.14 +/- 0.08 (p = 0.0025); transpulmonary gradient 12 +/- 3 to 9 +/- 3 (p = 0.05). A significant increase was also found in cardiac index from 4.2 +/- 1.1 to 4.9 +/- 1.4 (p = 0.0007). Other parameters such as mean pulmonary, systemic, wedge and right atrial pressures, in addition to intrapulmonary shunting, heart rate, and oxygen extraction ratio, did not present any significant changes. The procedure was well tolerated by all patients, and no undesirable effects such as methemoglobin elevation or worsening of pulmonary hypertension after nitric oxide suspension were observed. CONCLUSIONS: The beneficial effects observed by inhaled nitric oxide in the pulmonary vascular resistance index/systemic vascular resistance index ratio, transpulmonary gradient, and cardiac index suggest that nitric oxide acts mainly in pulmonary territory and could be a possible pulmonary vasodilator agent used to control central hemodynamics after heart transplantation.

Forced swim stress: supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline and the role of corticosterone.

1. Forced swim (three daily sessions) resulted in an increased plasma corticosterone level and supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline. 2. Bilateral adrenalectomy, performed 2 days before forced swim, abolished the development of pacemaker supersensitivity to isoprenaline. 3. Administration to rats of the antiglucorticoid compound RU-38486 prevented the development of pacemaker supersensitivity to isoprenaline. Pretreatment of rats not submitted to forced swim with the synthetic glucocorticoid RU-28362 causes pacemaker supersensitivity to isoprenaline. 4. Pretreatment of rats with diazepam or imipramine which block the forced swim-induced increase in the plasma level of corticosterone prevented the development of pacemaker supersensitivity to isoprenaline. 5. It is concluded that corticosterone plays a critical role in the modulation of the sensitivity to catecholamines of the pacemaker beta-adrenoceptors during adaptation to repeated stress.

[Comparison of negative chronotropic action of nitrendipine, nifedipine and verapamil on the isolated right atrium of normotensive and renovascular hypertensive rats]. / Comparação do cronotropismo negativo da nitrendipina, nifedipina e verapamil no átrio direito isolado de ratos normotensos e com hipertensão renovascular.

PURPOSE: To study the negative chronotropic effects of nitrendipine, nifedipine and verapamil in isolated right atria from normotensive and renovascular hypertensive rats. MATERIAL AND METHODS: Hypertension (medium arterial pressure, MAP = 154 +/- 4 mmHg) was induced by applying a silver clip to the left renal artery and right nephrectomy. Control rats (MAP = 109 +/- 2 mmHg) were submitted to right nephrectomy only. The animals were studied 2 weeks after surgery. Different preparations were used to obtain cumulative dose-response curves (0.01 microM to 100 microM) with each drug. RESULTS: No difference in "in vitro" initial sinusal rate of control (243 +/- 7 bpm) and hypertensive (245 +/- 5 bpm) rats was observed. The negative chronotropic response produced by calcium channel blockers was similar in normotensive and hypertensive groups. 2 microM verapamil, 4 microM nitrendipine or 20 microM nifedipine was necessary to produce a 50% decrease of the initial sinusal rate. CONCLUSION: Sensitivity of the sinusal pacemaker to calcium antagonists does not change in this model of hypertension. Moreover, the negative chronotropic effect of nitrendipine is stronger than nifedipine and weaker than verapamil.

Comparaçäo do cronotropismo negativo da nitrendipina, nifedipina e verapamil no átrio direito isolado de ratos normotensos e com hipertensäo renovascular / Nitrendipine, nifedipine and verapamil: a comparison of the negative chronotropic effects using the isolated right atria from no rmote n sive and re nova s cular hypertensive rats.

Estudar o efeito cronotrópico negativo de nitrendipina, nifedipina e verapamil no átrio direito isolado de ratos normotensos e com hipertensäo renovascular. A hipertensäo foi produzida pela implantaçäo de anel de prata na artéria renal esquerda e nefrectomia direita. Os animais foram estudados 15 dias após a cirurgia, quando a PA média (medida diretamente, no animal acordado, através de cânula intravascular) do grupo hipertenso (154 ñ 4 mm Hg) era maior que a do grupo controle (109 ñ 2 mmHg). A freqüência atrial "in vitro" foi determinada a partir dos registros das contraçöes isométricas. Atrios diferentes foram usados para se obter as curvas dose-resposta (0,01 micronM - 100 micronM) de cada droga. A freqüência atrial "in vitro" foi idêntica nos normotensos (243 ñ 7 bpm) e hipertensos (245 ñ 5 bpm). A sensibilidade às drogas testadas também foi a mesma, em ambos os grupos. A concentraçäo de droga necessária para reduzir 50% da freqüência sinusal foi cerca de 2 micronM para o verapamil, 4 micronM para a nitrendipina e 20 micronM para a nifedipina. A hipertensäo näo altera a sensibilidade do marca-passo sinusal aos bloqueadores de canal de cálcio. O efeito cronotrópico negativo da nitrendipina é intermediário entre o do verapamil e o da nifedipina