Maricene Sabha

Transdermal nicotine mimics the smoking‐induced endothelial dysfunction*

Cigarette smoking is a major risk factor for coronary artery disease and causes endothelial dysfunction, perhaps by decreasing the availability of nitric oxide availability in arteries and veins. Nicotine in cigarette smoke may be responsible for this impaired endothelial response.

Intensive Monitoring of Adherence to Treatment Helps to Identify “True” Resistant Hypertension

Intensive monitoring of adherence in patients with uncontrolled hypertension was evaluated over a 6‐month period. After that period, only patients well characterized as having resistant hypertension were followed for 12 months. The goal of this study was to evaluate whether adherence to a drug regimen helps to identify patients with resistant hypertension. Forty‐four hypertensive patients resistant to a 3‐drug regimen (average blood pressure [BP] mm Hg, mean ± standard deviation) were studied prospectively. Each patient was followed for a 12‐month period. Adherence to treatment was evaluated through self‐report, applying Morisky’s questionnaire and the pill count method. Ambulatory BP monitoring and office BP measures were performed. By pill count, 63.6% of the patients were adherent to treatment at the start of the survey and 94% at the end, although 59% of the patients still did not reach normal BP levels. We found that non‐adherence was not associated with resistance to antihypertensive treatment. Therefore, after investigation, we concluded that patients who presented with uncontrolled arterial BP may be truly resistant hypertensive to treatment.

Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers.

Smoking potentiates the enhanced cardiovascular risk of hypertensive patients. Although nicotine replacement therapy is safe when used by healthy individuals to quit smoking, there is no evidence that nicotine replacement therapy is safe in hypertensive smokers. In this crossover, single-blinded, placebo-controlled study, we compared for 4 h the acute effects of transdermal nicotine on the mean arterial pressure (MAP) and heart rate (HR) of mildly hypertensive smokers treated with hydrochlorothiazide with the responses in normotensive smokers and nonsmokers monitored with Finapres and ambulatory blood pressure systems. The plasma concentrations of thromboxane B2 (TXB2, the stable breakdown product of TXA2) were also measured by ELISA to assess whether transdermal nicotine acutely affects TXA2 production. The use of 21-mg nicotine patches increased the MAP and HR in nonsmokers (from 94+/-4 mm Hg and 69+/-3 beats/min to 117+/-7 mm Hg and 83+/-3 beats/min, respectively; P < .05) as well as the MAP in normotensive smokers (from 83+/-4 to 106+/-7 mm Hg; P < .05). However, MAP and HR remained unaltered in hypertensive smokers after transdermal nicotine. Higher basal TXB2 levels were observed in hypertensive smokers compared with normotensive smokers and nonsmokers (2019+/-402 v 670+/-167 and 556+/-68 pg/mL, respectively; P < .05). Transdermal nicotine increased the TXB2 levels only in nonsmokers (P < .05). These data indicate that the use of transdermal nicotine in mildly hypertensive smokers is probably safe. Further studies involving other classes of hypertensive patients are warranted.

Blood pressure circadian rhythm and endothelial function in heavy smokers: acute effects of transdermal nicotine.

Nicotine replacement therapy appears to be safe when used by healthy patients to aid in smoking cessation; however, the immediate acute effects of nicotine replacement therapy on the circadian rhythm of blood pressure (BP) and endothelial function in heavy smokers are not well understood. Twenty‐six heavy smokers were requested to stop smoking for 48 hours. BP and heart rate were recorded over 48 hours by ambulatory BP monitoring, with beat‐to‐beat changes being monitored for the first 10 hours by a noninvasive finger device. The reactivity of the brachial artery was evaluated using flow‐mediated dilation immediately after smoking cessation, before the application of a 21‐mg nicotine patch or placebo patch, and 24 hours after patch placement. Transdermal nicotine caused a mild but significant elevation in BP in the early morning in 21 of 26 volunteers. The decrease in nocturnal BP was attenuated in patients with the nicotine patch compared with the placebo patch; this was associated with impaired endothelium‐dependent vasodilation.

T allele of -344C/T polymorphism in aldosterone synthase gene is not associated with resistant hypertension

Resistant hypertension (RH) is the maintenance of elevated blood pressure concurrent with the use of three different anti-hypertensive drugs, one of which is a diuretic. The Renin-Angiotensin-Aldosterone System plays a major role in volume-dependent hypertension. Therefore, its components are interesting targets for genetic association studies. This work focused on the −344 C/T polymorphism in the CYP11b2 gene, which encodes aldosterone synthase. This work evaluates the association between T allele and resistance to anti-hypertensive treatment. Genotyping analysis included 88 subjects with RH, 142 who were responsive to anti-hypertensive treatment and 110 subjects as a control group. Plasmatic concentrations of aldosterone, renin and cortisol, carotid intima-media thickness and carotid-femoral pulse wave velocity were assessed in a smaller subset of hypertensive patients. An association was found between T allele and hypertension (P<0.005), but there was no difference in allele frequencies between both hypertensive groups. There was no difference in plasmatic parameters either, in remodeling indicators between the genotypic groups.

Acute effects of pharmacotherapies in blood pressure in normotensive moderate smokers

Abstract This study was designed to evaluate the changes in arterial blood pressure (BP) and heart rate (HR) in moderate smokers during smoking abstinence after 7 days of treatment with bupropion alone, transdermal nicotine or bupropion combined with transdermal nicotine. Twenty-four healthy moderate smokers (12 female/12 male; 40±7 years) were evaluated randomly on five occasions and their systolic, diastolic, mean arterial blood pressure (MAP) and HR were measured by a Finapres device for 10 h, immediately after smoking interruption. All of the 24 smokers participated on five protocols during 7 days: control group (C) – no drugs; placebo group (PL); bupropion group (BUP) 150–300 mg; transdermal nicotine group (TN) – 21 mg; and BUP+TN-nicotine patch. Concomitantly, the subjects were evaluated by ABPM (ambulatory BP monitoring). All of BP parameters monitored shown significant statistical differences in the BUP, TN and BUP+TN groups compared with the controls (p<0.05), when measured by Finapres. The HR remained unaltered in all of the groups. No significant differences were seen in the BP or HR during the 24-h ABPM. These findings indicate that in moderate smokers, bupropion, transdermal nicotine or bupropion associated with transdermal nicotine caused an elevation in the BP after acute smoking interruption.

Hemodynamic Effects Of A Combination Of Bupropion And Nicotine In Anesthetized Dogs.

Bupropion has been used to treat psychic depression and as a therapy for smoking cessation, the latter mainly in association with nicotine. However, there have been no detailed studies of the hemodynamic effects of the association of bupropion with nicotine during replacement therapy. In this study, we evaluated the effects of such an association on the cardiovascular parameters in anesthetized dogs. Bupropion, either alone or together with nicotine, had no significant effect on the cardiac index (Cl; 4.7±0.2 vs 4.3±0.1 and 3.5±0.3 vs 3.4±0.3 L.min−1.m2, respectively; mean±SEM) and mean arterial pressure (MAP; 134±5.0 vs 145±11.0 and 118±5.0 vs 133±10.5 mmHg, respectively). There was a slight but significant increase in the systemic vascular resistance index (SVRI; 2165±93 vs 2645±126 and 2335±100 vs 2737±200 dyn.cm−5m−2, respectively). However, there was a significant increase in the mean pulmonary artery pressure (MPAP; 20±0.8 vs 25±1.6 and 18±1.3 vs 25±1.6 mmHg, respectively; p<0.05) and pulmonary vascular resistance index (IRVP; 194±11 vs 272±21 and 206±32 vs 307±42 dyn.cm−5m−2, respectively; p<0.05). These results show that bupropion alone or in association with nicotine does not markedly affect most hemodynamic parameters of the systemic circulation, although the significant increase in MPAP and IRVP can elevate the pulmonary pressure.

Infusão intravenosa de vasopressina causa efeitos cardiovasculares adversos dose-dependentes em cães anestesiados

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.FUNDAMENTO: A arginina-vasopressina (AVP) tem sido amplamente utilizada no tratamento do choque vasodilatador. Entretanto, ha muitas questoes relativas ao seu uso clinico, especialmente em altas doses, pois sua utilizacao pode estar associada a efeitos cardiacos adversos. OBJETIVO: Investigar os efeitos cardiovasculares da AVP em infusao IV continua nos parâmetros hemodinâmicos em caes. METODOS: Dezesseis caes saudaveis sem raca definida, anestesiados com pentobarbital, receberam um cateter intravascular e foram aleatoriamente designados para dois grupos: controle (solucao salina - placebo; n=8) e AVP (n=8). O grupo do estudo recebeu infusao de AVP por tres periodos consecutivos de 10 minutos a doses logaritmicamente progressivas (0,01; 0,1 e 1,0 U/kg/min), a intervalos de 20 minutos. A frequencia cardiaca (HR) e as pressoes intravasculares foram continuamente registradas. O debito cardiaco foi medido atraves do metodo de termodiluicao. RESULTADOS: Nenhum efeito hemodinâmico significante foi observado durante a infusao de 0,01 U/kg/min de AVP, mas com as doses mais altas, de 0,1 e 1,0U/kg/min, houve um aumento progressivo na pressao arterial media (PAM) e indice de resistencia vascular sistemica (IRVS), com significante diminuicao na frequencia cardiaca (FC) e indice cardiaco (IC). Com a dose de 1,0 U/kg/min, tambem foi observado um aumento significante no indice de resistencia vascular pulmonar (IRVP), principalmente devido a diminuicao no IC. CONCLUSAO: A AVP em doses entre 0,1 e 1,0 U/kg/min resultou em significantes aumentos na PAM e no IRVS, com efeitos inotropicos e cronotropicos negativos em animais saudaveis. Embora essas doses sejam de 10 a 1.000 vezes maiores do que as rotineiramente utilizadas no tratamento do choque vasodilatador, nossos dados confirmam que a AVP deveria ser usada cuidadosamente e sob rigida monitoracao hemodinâmica na pratica clinica, especialmente se doses maiores do que 0,01 U/kg/min forem necessarias.

Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.FUNDAMENTO: A arginina-vasopressina (AVP) tem sido amplamente utilizada no tratamento do choque vasodilatador. Entretanto, ha muitas questoes relativas ao seu uso clinico, especialmente em altas doses, pois sua utilizacao pode estar associada a efeitos cardiacos adversos. OBJETIVO: Investigar os efeitos cardiovasculares da AVP em infusao IV continua nos parâmetros hemodinâmicos em caes. METODOS: Dezesseis caes saudaveis sem raca definida, anestesiados com pentobarbital, receberam um cateter intravascular e foram aleatoriamente designados para dois grupos: controle (solucao salina - placebo; n=8) e AVP (n=8). O grupo do estudo recebeu infusao de AVP por tres periodos consecutivos de 10 minutos a doses logaritmicamente progressivas (0,01; 0,1 e 1,0 U/kg/min), a intervalos de 20 minutos. A frequencia cardiaca (HR) e as pressoes intravasculares foram continuamente registradas. O debito cardiaco foi medido atraves do metodo de termodiluicao. RESULTADOS: Nenhum efeito hemodinâmico significante foi observado durante a infusao de 0,01 U/kg/min de AVP, mas com as doses mais altas, de 0,1 e 1,0U/kg/min, houve um aumento progressivo na pressao arterial media (PAM) e indice de resistencia vascular sistemica (IRVS), com significante diminuicao na frequencia cardiaca (FC) e indice cardiaco (IC). Com a dose de 1,0 U/kg/min, tambem foi observado um aumento significante no indice de resistencia vascular pulmonar (IRVP), principalmente devido a diminuicao no IC. CONCLUSAO: A AVP em doses entre 0,1 e 1,0 U/kg/min resultou em significantes aumentos na PAM e no IRVS, com efeitos inotropicos e cronotropicos negativos em animais saudaveis. Embora essas doses sejam de 10 a 1.000 vezes maiores do que as rotineiramente utilizadas no tratamento do choque vasodilatador, nossos dados confirmam que a AVP deveria ser usada cuidadosamente e sob rigida monitoracao hemodinâmica na pratica clinica, especialmente se doses maiores do que 0,01 U/kg/min forem necessarias.

Infusión intravenosa de vasopresina causa efectos cardiovasculares adversos dependientes de la dosis en canes anestesiados

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.FUNDAMENTO: A arginina-vasopressina (AVP) tem sido amplamente utilizada no tratamento do choque vasodilatador. Entretanto, ha muitas questoes relativas ao seu uso clinico, especialmente em altas doses, pois sua utilizacao pode estar associada a efeitos cardiacos adversos. OBJETIVO: Investigar os efeitos cardiovasculares da AVP em infusao IV continua nos parâmetros hemodinâmicos em caes. METODOS: Dezesseis caes saudaveis sem raca definida, anestesiados com pentobarbital, receberam um cateter intravascular e foram aleatoriamente designados para dois grupos: controle (solucao salina - placebo; n=8) e AVP (n=8). O grupo do estudo recebeu infusao de AVP por tres periodos consecutivos de 10 minutos a doses logaritmicamente progressivas (0,01; 0,1 e 1,0 U/kg/min), a intervalos de 20 minutos. A frequencia cardiaca (HR) e as pressoes intravasculares foram continuamente registradas. O debito cardiaco foi medido atraves do metodo de termodiluicao. RESULTADOS: Nenhum efeito hemodinâmico significante foi observado durante a infusao de 0,01 U/kg/min de AVP, mas com as doses mais altas, de 0,1 e 1,0U/kg/min, houve um aumento progressivo na pressao arterial media (PAM) e indice de resistencia vascular sistemica (IRVS), com significante diminuicao na frequencia cardiaca (FC) e indice cardiaco (IC). Com a dose de 1,0 U/kg/min, tambem foi observado um aumento significante no indice de resistencia vascular pulmonar (IRVP), principalmente devido a diminuicao no IC. CONCLUSAO: A AVP em doses entre 0,1 e 1,0 U/kg/min resultou em significantes aumentos na PAM e no IRVS, com efeitos inotropicos e cronotropicos negativos em animais saudaveis. Embora essas doses sejam de 10 a 1.000 vezes maiores do que as rotineiramente utilizadas no tratamento do choque vasodilatador, nossos dados confirmam que a AVP deveria ser usada cuidadosamente e sob rigida monitoracao hemodinâmica na pratica clinica, especialmente se doses maiores do que 0,01 U/kg/min forem necessarias.