Effects of intraoperative diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery / Efeitos da infusão intraoperatória de diltiazem sobre as mudanças do fluxo em enxertos arteriais e venosos em cirurgia de revascularização do miocárdio

AbstractObjective:This study aimed to show the effects of intra-operative diltiazem infusion on flow in arterial and venous grafts in coronary artery bypass graft surgery.Methods:Hundred fourty patients with a total of 361 grafts [205 (57%) arterial and 156 (43%) venous] underwent isolated coronary surgery. All the grafts were measured by intraoperative transit time flow meter intra-operatively. Group A (n=70) consisted of patients who received diltiazem infusion (dose of 2.5 microgram/kg/min), and Group B (n=70) didn't receive diltiazem infusion.Results:Mean graft flow values of left internal mammary artery were 53 ml/min in Group A and 40 ml/min in Group B (P<0.001). Pulsatility index (PI) values of left internal mammary artery for Group A and Group B were 2.6 and 3.0 respectively (P<0.001). No statistically significant difference was found between venous graft parameters.Conclusion:We recommend an effect of diltiazem infusion in increasing graft flows in coronary artery bypass graft operations.

ResumoObjetivo:Este estudo teve como objetivo mostrar os efeitos da infusão de diltiazem intraoperatória no fluxo arterial e enxertos venosos em cirurgia de revascularização do miocárdio.Métodos:Cento e quarenta pacientes com um total de 361 enxertos [205 (57%) arteriais e 156 (43%) venosos] passaram por uma cirurgia coronária isolada. Todos os enxertos foram medidos pelo medidor de fluxo de tempo de trânsito intraoperatório. Grupo A (n=70), formado por pacientes que receberam infusão de diltiazem (dose de 2,5 micrograma/kg/min), e Grupo B (n=70), por aqueles que não receberam infusão de diltiazem.Resultados:Os valores médios de fluxo de enxerto de artéria mamária interna esquerda foram 53 ml/min no grupo A e 40 ml/min no Grupo B (P<0,001). Valores do índice de pulsatilidade da artéria mamária interna esquerda para o Grupo A e do Grupo B foram de 2,6 e 3,0, respectivamente (P<0,001). Não houve diferença estatisticamente significativa entre os parâmetros do enxerto venoso.Conclusão:Sugerimos um efeito da infusão de diltiazem em aumentar os fluxos de enxerto em operações de bypass de artéria coronária.

Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart / Efeitos da isquemia e pré-condicionamento com omeprazol na recuperação funcional do coração isolado de rato

Abstract Objective: The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion. Methods: The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG) after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped) for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC) were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC) hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion. Results: Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion. Conclusion: Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible. .

Resumo Objetivo: O objetivo deste estudo foi comparar os efeitos protetores de efeitos protetores isquêmicos e potenciais de précondicionamento farmacológico com omeprazol no coração isolado de rato submetido à isquemia/reperfusão. Métodos: Os corações de ratos albinos Wistar machos foram excisados e perfundidos em um aparelho de Langendorff. No grupo controle (grupo I), após o período de estabilização, os corações foram submetidos à isquemia global (a perfusão foi totalmente interrompida) por 20 minutos e 30 minutos de reperfusão. Corações do grupo II (IPC) foram submetidos a précondicionamento isquêmico com duração de 5 minutos antes de 20 minutos de isquemia e 30 minutos de reperfusão. No terceiro grupo (OPC), corações foram submetidos a pré-condicionamento com duração de 5 minutos com 100 μM de omeprazol, e, então, submetidos a 20 minutos de isquemia e 30 minutos de reperfusão. Resultados: A administração de omeprazol antes da indução da isquemia teve efeito protetor sobre a recuperação funcional do miocárdio especialmente em relação aos valores de pressão sistólica ventricular esquerda e dp/dt max. Também os nossos achados são de que os valores de fluxo coronário não se alteraram entre os grupos OPC e IPC no último ponto de reperfusão. Conclusão: Com base nos nossos resultados, o pré-condicionamento isquêmico poderia ser usado como primeira janela de proteção após a lesão isquêmica, especialmente porque todos os parâmetros analisados apresentam tendência contínua de recuperação da função do miocárdio. Por outro lado, o pré-condicionamento induzido com omeprazol apresenta tendência repentina de recuperação com proteção miocárdio positiva, embora menos efetiva da obtida com o pré-condicionamento isquêmico. Devemos considerar que o omeprazol pode ser usado em muitas circunstâncias clínicas em que o pinçamento coronariano direto para pré-condicionamento isquêmico não é possível. .

Adenosina intracoronaria durante la angioplastía primaria para la preservación del flujo coronario / Intracoronary adenosine during primary angioplasty and coronary flow preservation

Introducción: El uso de adenosina intracoronario durante la angioplastía coronaria ha sido controversial en los últimos años. El beneficio teórico en el flujo epi-cárdico y microcirculatorio (MC) no se ha demostrado categóricamente en estudios clínicos. Objetivo: Evaluar el efecto de protección de la MC y del flujo epicárdico al utilizar adenosina intracoronaria durante la AP. Métodos: Estudio clínico randomizado multicéntrico, caso-control con análisis post hoc ciego, en pacientes portadores de SCA con SDST. Un total de 122 pacientes aleatorizados 1:1, se consideró caso (A(+)) aquel que se administró adenosina en dosis de 120 microgramos intracoronario en bolo y luego infusión periférica de 6mg en 33ml de suero fisiológico a pasar en 2-3 minutos Se evaluaron criterios clínicos, angiográficos y electrocar-diográficos de reperfusión epicárdica y microvascular. Observadores ciegos evaluaron el conteo de cuadros TIMI (cTFC) y "blush" miocárdico (BM). Se compararon las características clínicas, angiográficas basales y los resultados angiográficos finales entre ambos grupos, usando t-Student, prueba de Mann-Whitney, Chi cuadrado y test exacto de Fisher según correspondiera. En todos los pacientes se evaluó la resolución del SDST con el score de ST. Además, se evaluó las posibles complicaciones por uso de adenosina intracoronaria. Resultados: Entre 2012-2014 se reclutaron 122 pacientes. Al comparar las características basales entre el grupo A(+) vs los A(-) no hubo diferencias significativas en la edad (59+/-10 años para A(+) vs 58+/-10 años para A(-), p:0,97), ni en las comorbilidades. Al comparar las características angiográficas basales, no se encontró diferencias en los vasos culpables (ADA 44% en A(+) vs 43% en A(-), p:0.57), en las cargas trombóticas (Alta carga: 69% para A(+) vs 74% para A(-), p:0.53), en el flujo TIMI pre (TIMI 0-1 86% para ambos grupos, p:0,69), cTFC pre (87+/-23 cuadros en A(+) vs 88+/-25 cuadros en A(-), p:0.99), Killip de ingreso (Killip I, 86% para A(+) vs 76% para A(-), p:0,11) y fracción de eyección (51+/-8% para A(+) vs 48+/-9% para (-), p:0,61). Al evaluar los resultados angiográficos finales encontramos diferencias significativas en el flujo TIMI (TIMI 3 96% para grupo A(+) vs 74% para grupo A(-), p:0,002). No encontramos diferencias significativas en el BM (Blush 3 73% para ambos grupos, p:0.74), el cTFC final (24+/-11 cuadros en A(+) vs 26+/-12 cuadros en A(-), p:0,85). Si consideramos cTFC <23cuadros como éxito angiográficos, tampoco encontramos diferencias significativas (56% para A(+) vs 53% para A(-), p:0,45). Por último tampoco hubo diferencias significativas con la resolución del segmento ST (44% para A(+) vs 58% para A(-), p:0,126). Conclusión: De acuerdo a los resultados obtenidos podemos inferir que la adenosina intracoronaria cumple un rol en la conservación óptima del flujo epicárdico coronario, pero sin influir en la microcirculación. Mayores estudios se requieren para determinar si se traduce en algún beneficio clínico.

Background: The effect of Intracoronary adenosine for coronary flow preservation during primary PTCA is debatable. Clinical studies have not established a benefit of adenosine administration upon epicar-dic or microcirculatory flows. Aim: to evaluate micro circulatory flow preservation after administration of intracoronary adenosine during primary PTCA. Method: From 2012 to 2014, 122 patients with ST elevation myocardial infarction randomized to either adenosine of control (2:1) were included in a controlled clinical trial. Adenosine was administered in a 120 mg bolus followed by 6mg solution during 2 to 3 min. Epicardic and micro vascular flows were evaluated through clinical, angiographic, electrocardiographic and reperfusion variables. TIMI (cTFC) and myocardial "blush" were measured by blind observers. Results: Basal characteristics, namely age and co-morbidities were similar between groups. Also, the distribution of coronary vessels involved in MI was similar with a preponderance of the LAD artery. There was an high proportion of patients with an elevated thrombus load (Adenosine 69%, controls 74%) ; TIMI flow 0-1 was 86% in both groups and TIMI cTFC was not different (adenosine: 87±23 , controls 88±25 ). Over 75% of patients were Killip I, and the ejection fraction was slightly decreased (adenosine 51±8% , controls 48±9% , NS). In contrast, TIMI flow was significantly greater for adenosine (TIMI 3 96% for adenosine and 74% for controls, p=0.002). No difference was observed in myocardial blush (B 3 73% in both groups) nor cTFC (24±11 vs. 26±12, respectively). Finally, regression of ST elevation was similar in both groups. Conclusion: Intracoronary adenosine during PTCA in ST elevation MI was associated to a better epicardial but not microvascular flow. Further study is needed to evaluate the eventual clinical benefit of these effects.

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E2; 5 µg·100 g-1·day-1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

A eficácia da terlipressina versus adrenalina na ressuscitação cardiopulmonar em suínos / The efficacy of terlipressin versus adrenaline in swine cardiopulmonary resuscitation / La eficacia de la terlipresina versus adrenalina en la resucitación cardiopulmonar en cerdos

JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi avaliar a eficácia da terlipressina (TP) versus adrenalina (ADR) em aumentar a pressão de perfusão coronariana (PPC) e o retorno da circulação espontânea (RCE) na RCP em suínos. MÉTODOS: Sob anestesia cetamina/tiopental, induziu-se fibrilação ventricular em 44 porcos fêmeas imaturos, permanecendo não assistida por 10 min, seguidos de 2 min de RCP-manual (100 compressões/10 ventilações/min com ar). Os animais foram então alocados em quatro grupos, recebendo: 1) ADR (45 µg.kg-1); 2) salina-placebo (10 mL); 3) TP (20 µg.kg-1); 4) TP (20 µg.kg-1) + ADR (45 µg.kg-1). Desfibrilação foi realizada 2 min após, observando-se os animais sobreviventes por um período de 30 min. ECG, PA sistêmica, PAD e PetCO2 foram monitorados continuamente. RESULTADOS: A TP não diferiu do placebo quanto aos efeitos na PPC, com baixas taxas de RCE em ambos os grupos (1/11 vs.2/11; p = NS). A ADR aumentou a PPC de 13 ± 12 para 54 ± 15 mmHg (p < 0,0001), efeito similar a TP + ADR (de 21 ± 10 para 45 ± 13 mmHg; p < 0,0001), com altas taxas de RCE/sobreviventes em ambos os grupos (10/11 vs.9/11, respectivamente). Entre os sobreviventes, maior PAM foi observada no grupo TP + ADR vs.ADR (105 ± 19 mmHg vs.76 ± 21 mmHg; p = 0,0157). CONCLUSÕES: ADR e TP + ADR foram efetivas para aumentar a PPC/RCE neste modelo experimental, mas a TP, isolada, não foi diferente do placebo. Contudo, nos animais sobreviventes do grupo TP + ADR observou-se maior estabilidade hemodinâmica após a RCE, sugerindo que a TP possa ser uma medicação útil no manuseio da hipotensão pós-RCP.

BACKGROUND AND OBJECTIVES: The objective of the present study was to evaluate the efficacy of terlipressin (TP) vs.adrenaline (ADR) in increasing coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) in swine CPR. METHODS: Under anesthesia with ketamine/thiopental, ventricular fibrillation was induced in 44 female immature pigs, remaining unassisted for 10 minutes, followed by 2 minutes of manual CPR (100 compression/10 ventilations/min with air). Animals were, then, divided into four groups: 1) ADR (45 µg.kg-1); 2) saline-placebo (10 mL); 3) TP 20 µg.kg-1); and TP (20 µg.kg-1) + ADR (45 µg.kg-1). Defibrillation was performed after 2 minutes, observing surviving animals for a 30-minute period. Electrocardiogram, systemic BP, DBP, and PetCO2 were monitored continuously. RESULTS: Terlipressin did not differ from placebo regarding the effects on CPP, with low rates of ROSC in both groups (1/11 vs.2/11; p = NS). Adrenaline increased CPP from 13 ± 12 to 54 ± 15 mmHg (p < 0.0001), similar effect to TP + ADR (from 21 ± 10 to 45 ± 13 mmHg; p < 0.0001), with high rates of ROSC/survivors in both groups (10/11 vs.9/11, respectively). Among survivors, greater MAP was observed in the TP + ADR group vs.ADR (105 ± 19 mmHg vs.76 ± 21 mmHg; p = 0.0157) groups. CONCLUSIONS: Adrenaline and TP + ADR were effective on maintaining CPP/ROSC in this experimental model, but isolated TP did not differ from placebo. However, in surviving animals in the TP + ADR group, greater hemodynamic stability was observed after ROSC, suggesting that TP can be a useful medication in the management of post-CPR hypotension.

JUSTIFICATIVA Y OBJETIVOS: El objetivo de este estudio fue evaluar la eficacia de la terlipresina (TP) versus adrenalina (ADR) en aumentar la presión de perfusión coronaria (PPC) y el retorno de la circulación espontánea (RCE) en la RCP en cerdos. MÉTODOS: Bajo la anestesia ketamina/tiopental, se indujo la fibrilación ventricular en 44 cerdos hembras no adultos, permaneciendo no asistida por 10 min, seguidos de 2 min de RCP-manual (100 compresiones/10 ventilaciones/min con aire). Los animales se ubicaron entonces en cuatro grupos, recibiendo: 1) ADR (45 µg.kg-1); 2) salina-placebo (10 mL); 3) TP (20 µg.kg-1); 4) TP (20 µg.kg-1) + ADR (45 µg.kg-1). La desfibrilación fue realizada 2 min después, haciendo el seguimiento de los animales sobrevivientes por un período de 30 min. ECG, PA sistémica, PAD y PetCO2 fueron monitorizados continuamente. RESULTADOS: La TP no fue diferente del placebo en cuanto a los efectos en la PPC, con bajas tasas de RCE en ambos grupos (1/11 vs.2/11; p = NS). La ADR aumentó la PPC de 13 ± 12 para 54 ± 15 mmHg (p < 0,0001), efecto similar a TP + ADR (de 21 ± 10 para 45 ± 13 mmHg; p < 0,0001), con altas tasas de RCE/supervivientes en ambos grupos (10/11 vs.9/11, respectivamente). Entre los supervivientes, se observó una mayor PAM en el grupo TP + ADR vs.ADR (105 ± 19 mmHg vs.76 ± 21 mmHg; p = 0,0157). CONCLUSIONES: La ADR y TP + ADR fueron efectivas para aumentar la PPC/RCE en este modelo experimental, pero la TP aislada, no fue diferente del placebo. Sin embargo, en los animales supervivientes del grupo TP + ADR, vimos una mayor estabilidad hemodinámica después de la RCE, lo que nos indica que la TP puede ser una medicación útil en el manejo de la hipotensión post-RCP.

Função endotelial vascular em pacientes com fluxo coronário lento e os efeitos do nebivolol / Vascular endothelial function in patients with coronary slow flow and the effects of nebivolol

FUNDAMENTO: A função endotelial braquial tem sido associada ao fluxo lento coronário (FLC). O aumento do fluxo sanguíneo para a artéria braquial faz com que o endotélio libere óxido nítrico (ON), com subsequente vasodilatação. Além de sua atividade com betabloqueador, o nebivolol provoca vasodilatação, aumentando a liberação endotelial de ON. OBJETIVO: Avaliar os efeitos do nebivolol na função endotelial vascular em pacientes com FLC. MÉTODOS: 46 pacientes com FLC e 23 indivíduos com artérias coronárias epicárdicas normais foram examinados com ecocardiografia transtorácica e ultrassonografia da artéria braquial. Os pacientes foram reavaliados dois meses após o tratamento com aspirina ou aspirina e nebivolol. RESULTADOS: Os pacientes com FLC apresentaram maior índice de massa corporal (26,5 ± 3,3 vs. 23,8 ± 2,8, p < 0,001), tempo de relaxamento isovolumétrico (TRIV) de influxo mitral (114,9 ± 18,0 vs. 95,0 ± 22,0 mseg, p < 0,001), menor fração de ejeção do ventrículo esquerdo (FEVE) (63,5 ± 3,1 por cento vs. 65,4 ± 2,2, p = 0,009), colesterol HDL (39,4 ± 8,5 vs. 45,8 ± 7,7 mg/dL, p = 0,003) e dilatação fluxo-mediada da artéria braquial (DFM) (6,1 ± 3,9 por cento vs. 17,6 ± 4,5 por cento, p <0,001). Houve correlações significativas entre a DFM e a presença de FLC (r = 0,800, p < 0,001) e o colesterol HDL (r = 0,349, p = 0,003). Dos pacientes com FLC, apesar de os valores médios de DFM em pré-tratamento terem sido semelhantes (6,1 ± 4,3 por cento vs. 6,0 ± ,6 por cento, p = 0,917), em comparação com a DFM do grupo em pós-tratamento apenas com aspirina, a DFM apresentou valores significativamente maiores do que os pacientes tratados com aspirina e nebivolol (6,0 ± 3,5 por cento vs. 8,0 ± 2,9 por cento, p = 0,047). Constatou-se que o tratamento com nebivolol está associado a um significativo aumento na DFM (6,0 ± 3,6 a 8,0 ± 2,9 por cento, p = 0,030), ao passo que o tratamento apenas com aspirina não apresentou a mesma associação. CONCLUSÃO: A função endotelial pode ser comprometida nas artérias coronárias e braquiais em pacientes com FLC, e o nebivolol pode ser eficaz na melhora da função endotelial em pacientes com FLC.

BACKGROUND: Brachial endothelial function has been associated with coronary slow flow (CSF). Increasing blood flow to brachial artery provokes endothelium to release nitric oxide (NO) with subsequent vasodilatation. Besides its β1-blocker activity, nebivolol causes vasodilatation by increasing endothelial NO release. OBJECTIVE: To assess the effects of nebivolol on vascular endothelial function in patients with CSF. METHODS: Forty-six patients with CSF and 23 individuals with normal epicardial coronary arteries were examined with transthoracic echocardiography and brachial artery ultrasonography. The patients were reevaluated two months after treatment with aspirin or aspirin plus nebivolol. RESULTS: Patients with CSF had higher body mass index (26.5 ± 3.3 vs. 23.8 ± 2.8, p < 0.001), mitral inflow isovolumetric relaxation time (IVRT) (114.9 ± 18.0 vs. 95.0 ± 22.0 msec, p < 0.001) and lower left ventricular ejection fraction (LVEF) (63.5 ± 3.1 percent vs. 65.4 ± 2.2, p = 0.009), HDL-cholesterol (39.4 ± 8.5 vs. 45.8 ± 7.7 mg/dL, p = 0.003) and brachial flow-mediated dilatation (FMD) (6.1 ± 3.9 percent vs. 17.6 ± 4.5 percent, p < 0.001). There were significant correlations between FMD and the presence of CSF (r = 0.800, p < 0.001) and HDL-cholesterol (r = 0.349, p = 0.003). Among Patients with CSF, although pretreatment mean FMD values were similar (6.1 ± 4.3 percent vs. 6.0 ± ,6 percent, p = 0.917) compared to aspirin alone group, posttreatment FMD was significantly higher in patients treated with aspirin plus nebivolol (6.0 ± 3.5 percent vs. 8.0 ± 2.9 percent, p = 0.047). Treatment with nebivolol was associated with a significant increase in FMD (6.0 ± 3.6 to 8.0 ± 2.9 percent, p = 0.030) whereas treatment with aspirin alone was not. CONCLUSION: Endothelial function may be impaired in both coronary and brachial arteries in patients with CSF and nebivolol may be effective in the improvement of endothelial function in patients with CSF.

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR). Female SHR were divided into four groups (N = 7 each): sham-operated (SHAM), sham-operated and treated with tamoxifen (10 mg/kg) by gavage for 90 days (TAMOX), ovariectomized (OVX), and ovariectomized and treated with tamoxifen (OVX+TAMOX). Mean arterial pressure (MAP), heart rate (HR), coronary perfusion pressure (CPP), and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67 percent, respectively) in the OVX+TAMOX group compared to the OVX group (P < 0.01). The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg) when compared to the OVX group (P < 0.01) and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05). Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg) than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01). Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.

Preconditioning abolishion by midazolam in isolated hearts of rats / Abolição do precondicionamento pelo midazolam em corações isolados de ratos

PURPOSE: To study the effects of benzodiazepine midazolam in the coronary flow (Cflo), cardiac frequency (CF) and myocardial contractility in isolated hearts of rats subjected to ischemic preconditioning (IPC). METHODS: 30 Wistar rats were used, undistinguished by gender. After anesthesia with ethyl ether, the hearts were put into perfusion (Krebs-Henseleit solution, 95 percent O2 and 5 percent CO2, 37°C, 110-120mmHg), in disposable Langendorff type system. Five groups of six animals were constituted: GI- Control; GII- Ischemia; GIII- IPC; GIV- Ischemia + 100mcg of midazolam; GV- IPC + 100mcg of midazolam. After stabilization (t0), and on times t5, t10, t15, t20 and t25, CF, Cflo, systolic pressure (SP) and diastolic pressure (DP) and dP/dt were recorded. DP was maintained at 5 ± 2 mmHg. The statistical method ANOVA and Tukey Test were employed for p < 0.05. RESULTS: No significant variations have occurred between Cflo and CF. On Pd/td, differences have occurred (p<0.05) between groups I and II (respectively 94.7±23.0 and 62.3±12.1 percent). The preconditioning (GIII), improved significantly the results in the group II (respectively 62.3±12.1 and 87.1±12.4 percent). The decrease in dP/dt in group II was not prevented by midazolam (GIV) (62.3±12,1 and 60.5±15.8 percent). In group III, dP/dt was 87.1±12.4 percent, whereas in group V, only 55.5±17.2 percent (p<0.05) CONCLUSION: Midazolam, when administered before the ischemia, was unable to prevent the ischemic deterioration of the myocardium. When administered before the preconditioning, it has abolished its protective effect.

OBJETIVO: Estudar os efeitos do benzodiazepínico midazolam no fluxo coronariano (Fco), freqüência cardíaca (FC) e contratilidade miocárdica de corações isolados de ratos submetidos ao precondicionamento isquêmico (PCI). MÉTODOS: Foram utilizados 30 ratos Wistar sem distinção de sexo. Após anestesia com éter etílico, os corações foram postos em perfusão (solução de Krebs-Henseleit, 95 por cento de O2 e 5 por cento de CO2, 37°C, 110-120mmHg), em sistema tipo Langendorff descartável. Foram constituídos cinco grupos de seis animais: GI- Controle; GII- Isquemia; GIII- PCI; GIV- Isquemia + 100mcg de midazolam ; GV- PCI + 100mcg de midazolam. Após estabilização (t0), e nos tempos t5, t10, t15, t20 e t25, foram registrados a FC, Fco, pressões sistólica (PS) e diastólica (PD) e dP/dt. A PD foi mantida em 5 ± 2 mmHg. Empregou-se método estatístico ANOVA e Teste de Tukey para p < 0,05. RESULTADOS: Não ocorreram variações significantes entre FCo e FC. Na dP/dt, ocorreram diferenças (p<0,05) entre os grupos I e II (respectivamente 94,7±23,0 e 62,3±12,1 por cento). O precondicionamento (GIII), melhorou significantemente os resultados do grupo II (respectivamente 62,3±12,1 e 87,1±12,4 por cento). A queda da dP/dt no grupo II não foi impedida pelo midazolam (GIV) ( 62,3±12,1 e 60,5±15,8 por cento). No grupo III a dP/dT foi 87,1±12,4 por cento, sendo que no grupo V, apenas 55,5±17,2 por cento (p<0,05). CONCLUSÃO: O midazolan quando administrado antes da isquemia não impediu deterioração isquêmica do miocárdio. Quando administrado antes do precondicionamento aboliu seu efeito protetor.

Efeitos da N-acetilcisteína no precondicionamento isquêmico: estudo em corações isolados de ratos / Effects of n-acetylcysteine on ischemic preconditioning: study in isolated rat hearts

OBJETIVO: Avaliar se a N-Acetilcisteína (NAC) altera o Precondicionamento Isquêmico (PC) em corações isolados de ratos usando apenas um ciclo de PC. MÉTODOS: Freqüência Cardíaca (FC), Fluxo Coronariano (FLC) e Contratilidade Miocárdica (dP/dt) foram registradas em 30 corações de ratos Wistar. Após anestesia, os corações foram perfundidos em sistema de Langendorff com solução de Krebs-Hensleit (K-H), equilibrada (95 por cento de O2 e 5 por cento de CO2). GI: Controle (n=6); GII: 20 min. isquemia (n=6); GIII: PC (n=6); GIV 50 µg/ml/min NAC antes do PC (n =6); GV: 100 µg/ml/min NAC antes do PC (n=6). Todos os parâmetros foram mensurados após 15 minutos de estabilização (T0) e T3, T5, T10, T15, T20, T25 e T30 minutos de reperfusão. Significância estatística foi considerada quando P<0,05. RESULTADOS: Foram observadas alterações na FC comparando GI com GII em T20 e T25 e comparando GI com GIII e GIV com GV em T10 e T20 (P<0,05). FLC foi diferente comparando GI com GII em T3 e T5, GI com GIV em T10 e GI com GV em T10 e T25 (P<0,05). dP/dt foi semelhante comparando GIII com GI e GV. GIII apresentou maior dP/dt que GIV, mas sem diferença estatística (P>0,05). dP/dt foi maior no GV comparado com GIV, mas com diferença estatisticamente significativa somente em T30. CONCLUSÃO: Os corações precondicionados tiveram melhor dP/dt, sendo alteradas pelo uso de NAC no GIV e não alteradas no GV.

OBJECTIVE: The aim of this study is to assess if N-Acetylcysteine (NAC) changes the Ischemic Preconditioning (IP) in isolated rat hearts using only one cycle of IP. METHODS: Heart Rate (HR), Coronary Flow (CF) and Myocardial Contractility (dP/dt) were registered in 30 Wistar rat's hearts. After anesthesia the hearts were removed and perfused with Krebes-Hensleit equilibrated solution with 95 percent of O2 and 5 percent of CO2 according Langendorff's method. GI: Control (n=6); GII: 20 min. ischemia (n=6); GIII: IP (n=6); GIV 50 µg/ml/min NAC before IP (n =6); GV: 100 µg/ ml/min NAC before IP (n=6). Parameters were measured after 15 min. of stabilization (T 0) and T3, T5, T10, T15, T20, T25 and T30 min. after reperfusion. Statistical significance was considered when P<0.05. RESULTS: There were changes on HR comparing GI with GII at T20 and T25 and comparing GI with GIII, GIV with GV at T10 and T20 (P<0.05). CF was different comparing GI with GII at T3 and T5, GI with GIV at T10 and GI with GV at T10 and T25 (P<0.05). Myocardial Contractility was similar comparing GIII with GI and GV. GIII had higher dP/dt than GIV but without statistical difference (P>0.05). dP/dt was higher in GV than GIV but with statistically significant difference only at T30. CONCLUSION: dP/dt was better in preconditioned hearts and was changed if using NAC in GIV. The use of NAC didn't change the effects of preconditioning on myocardial contractility in GV.

Endothelial and non-endothelial coronary blood flow reserve and left ventricular dysfunction in systemic hypertension

OBJECTIVES: We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease. INTRODUCTION: Coronary blood flow reserve reduction has been proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction. METHODS: Eighteen hypertensive patients with normal epicardial coronary arteries on angiography were divided into two groups according to left ventricular fractional shortening (FS). Group 1 (FS >0.25): n=8, FS=0.29 ± 0.03; Group 2 (FS <0.25): n=10, FS= 0.17 ± 0.03. RESULTS: Baseline coronary blood flow was similar in both groups (Group 1: 80.15 ± 26.41 mL/min, Group 2: 100.09 ± 21.51 mL/min, p=NS). In response to adenosine, coronary blood flow increased to 265.1 ± 100.2 mL/min in Group 1 and to 300.8 ± 113.6 mL/min (p <0.05) in Group 2. Endothelium-independent coronary blood flow reserve was similar in both groups (Group 1: 3.31 ± 0.68 and Group 2: 2.97 ± 0.80, p=NS). In response to acetylcholine, coronary blood flow increased to 156.08 ± 36.79 mL/min in Group 1 and to 177.8 ± 83.6 mL/min in Group 2 (p <0.05). Endothelium-dependent coronary blood flow reserve was similar in the two groups (Group 1: 2.08 ± 0.74 and group Group 2: 1.76 ± 0.61, p=NS). Peak acetylcholine/peak adenosine coronary blood flow response (Group 1: 0.65 ± 0.27 and Group 2: 0.60 ± 0.17) and minimal coronary vascular resistance (Group 1: 0.48 ± 0.21 mmHg/mL/min and Group 2: 0.34 ± 0.12 mmHg/mL/min) were similar in both groups (p= NS). Casual diastolic blood pressure and end-systolic left ventricular stress were independently associated with FS. CONCLUSIONS: In our hypertensive patients, endothelium-dependent and endothelium-independent coronary blood flow reserve vasodilator administrations had similar effects in patients with either normal or decreased ...

Viabilidade miocárdica na lesão uniarterial: papel da ecocardiografia de estresse com dobutamina / Myocardial viability in a single-vessel disease: the role of a dobutamine stress echocardiography

OBJETIVO: Estudar um grupo de pacientes com lesão significativa em apenas uma artéria coronária e demonstrar se a ecocardiografia de estresse com dobutamina (EED) tem boa sensibilidade e especificidade na avaliação de viabilidade miocárdica nesse grupo de pacientes. MÉTODOS: Foram estudados 20 pacientes submetidos a angioplastia coronariana transluminal percutânea (ATC). Esse grupo foi avaliado 2 a 7 (3,65 ± 1,69) dias antes do procedimento, e 2 a 5 (4 ± 0,80) dias depois, realizando-se EED. Para a determinação de viabilidade miocárdica foi utilizado ecocardiograma bidimensional três meses após o procedimento. Doze pacientes foram submetidos a ATC de artéria descendente anterior (DA), 7 de artéria coronária direita (CD) e 1 de circunflexa (CX). Apenas um procedimento (CD) não obteve pleno êxito. RESULTADOS: Dos 340 segmentos estudados, 99 (29,18 por cento) demonstraram alterações contráteis, sendo 63 hipocinéticos (63,4 por cento), 28 acinéticos (28,28 por cento) e 8 discinéticos (8,08 por cento). Quanto aos segmentos envolvidos, obtivemos sensibilidade de 92,59 por cento, especificidade de 84,45 por cento, acurácia de 88,88 por cento para o exame EED. O único caso de ATC de CX demonstrou sensibilidade de 100 por cento; para DA, sensibilidade de 88,58 por cento, especificidade de 95 por cento e acurácia de 90,91 por cento. Para segmentos da CD, sensibilidade de 91,30 por cento, especificidade de 83,33 por cento e acurácia de 88,71 por cento. Todos os segmentos discinéticos eram inviáveis. Dos 63 hipocinéticos, a EED previu recuperação em 91,48 por cento. CONCLUSÃO: A EED é útil na avaliação de viabilidade miocárdica em pacientes com lesão significativa de apenas uma artéria.

Fisiología coronaria y su utilidad para el cardiólogo intervencionista: Medición invasiva de la presión y flujo coronarios / Coronary physiology and its usefulness for the interventionist cardiologist: Invasive measurement of coronary flow-pressure

Una de las más importantes limitaciones de la angiografía coronaria es su incapacidad para determinar el impacto fisiológico de las estenosis coronarias moderadas. La medición de la presión y del flujo sanguíneo coronario nos brinda información valiosa que complementa la evaluación anatómica y facilitan la toma de decisiones en el laboratorio de cateterismo cardíaco. En esta revisión se discuten los conceptos fundamentales de la fisiología coronaria, así como la metodología y aplicación clínica de las técnicas de medición de presión y flujo coronarios.

One of the most important limitations of coronary angiography is the inability to characterize the physiological significance of an intermediate coronary stenosis. Measuring coronary blood flow and pressure provides unique information that complements anatomic evaluation and facilitates decision-making in the cardiac catheterization unit. This review discusses the fundamental concepts of coronary physiology, methodology, and clinical applications of coronary and flow measurements.

Utilidad de la trimetazidina en la lesión por isquemia-reperfusión: Estudio experimental en un modelo canino de aturdimiento miocárdico / Usefulness of trimetazidine in ischemia-reperfusion lesion: experimental study in myocardial stunning model

Objetivo: Evaluar la acción de la trimetazidina en el deterioro de la función sistólica que se produce en el miocardio tras una isquemia única y prolongada. Métodos: Se analizaron 13 perros mestizos, de uno u otro sexo, asignados al azar a tratamiento oral con trimetazidina (6 perros) o placebo (7 perros) durante 7 días. Se realizó un protocolo de isquemia bajo anestesia consistente en una obstrucción completa de la arteria coronaria descendente anterior de 15 minutos de duración, seguida de 60 minutos de reperfusión. Las variables analizadas durante la obstrucción y la reperfusión fueron: Frecuencia cardíaca (FC), presión ventricular izquierda (PVI), dP/dt y las curvas de función regional de la zona isquémica y de una zona testigo (longitud telediastólica, telesistólica y fracción de acortamiento). Resultados: Las variables hemodinámicas (FC, PVI y dP/dt), no presentaron diferencias significativas entre ambos grupos, con poca variabilidad de sus valores respecto a los basales durante la isquemia-reperfusión. La fracción de acortamiento de la zona isquémica experimentó una disminución estadísticamente significativa durante la obstrucción coronaria en ambas series, alcanzando valores de discinesia, con persistencia de la disfunción contráctil tras 60 minutos de reperfusión, y sin diferencias entre ambas series (50% serie Placebo; 41% serie Trimetazidina). Conclusiones: La recuperación de la contractilidad miocárdica tras una isquemia completa en la serie tratada con TMZ no mostró diferencias significativas respecto a la serie Placebo, a diferencia de lo que ocurre con períodos de oclusión más cortos y repetidos.

Objective: The aim of this study is to evaluate the effect of trimetazidine (TMZ) on myocardial systolic dysfunction resulting from an isolated episode of induced coronary ischemia. Methods: In a double-blinded randomized design we studied 13 mongrel anesthetized dogs of either sex (6 of them treated with oral TMZ previously). The anterior descending coronary artery was totally occluded during 15 minutes followed by 60 minutes of reperfusion. Global and regional cardiac variables were recorded in control and ischemic areas. Results: There were no significant differences between TMZ and placebo series with respect to global cardiac function variables. Both series showed no significant variations in global variables during the ischemia-reperfusion process. The shortening fraction in the ischemic area fell significantly during the ischemic period in both TMZ and placebo series reaching dyskinetic values. Myocardial contractility dysfunction persisted after 60 minutes of reperfusion in both series with no significant differences (41% vs 50% placebo). Conclusions: Contrary to shorter and repeated occlusion periods, myocardial contractility recovery after a complete episode of ischemia did not show significant differences between TMZ-treated and placebo series.

Adenosine myocardial SPECT--its efficacy and safety and correlation with coronary angiogram.

OBJECTIVE: The aim of this study was to determine the safety and efficacy of adenosine Tc99m sestamibi myocardial perfusion study under controlled conditions and to correlate the adenosine Tc99m sestamibi perfusion defects and the coronary angiography in patients investigated for coronary artery disease. METHODS: This prospective study included 122 consecutive patients who underwent adenosine Tc99m sestamibi single photon emission computed tomography (SPECT) myocardial perfusion study. Seventy two patients had coronary angiographic correlation. All the patients who were referred by the cardiologists for stress myocardial perfusion scan who could not be stressed physiologically for one reason or the other were included in the study. RESULTS: Among the coronary angiography group the overall sensitivity, specificity, positive predictive value and negative predictive value of adenosine Tc99m sestamibi single photon emission computed tomography myocardial perfusion study for detecting significant coronary obstruction (diameter > or = 50%) were 94.4%, 79%, 85% and 92% respectively. The side effects were transient and required no treatment. CONCLUSION: We conclude adenosine Tc99m sestamibi single photon emission computed tomogram myocardial perfusion study is a reliable test with high sensitivity and specificity for the detection of coronary artery disease.

Nicardipine Augments Local Myocardial Perfusion after Coronary Artery Reperfusion in Dogs

Nicardipine is a potent coronary and systemic vasodilator without depression of ventricular function. We investigated the changes in local myocardial perfusion (LMP) according to the nicardipine administration after coronary reperfusion in a beating canine model. A Doppler probe was placed around the left anterior descending coronary artery (LAD) and thermal diffusion microprobe was implanted in the myocardium perfused by the exposed LAD. To define the nicardipine effects, we compared the two groups (control group, n=7 vs nicardipine group, n=7). In nicardipine group, 5 microgram/kg/min nicardipine was infused continuously. After the release of the LAD occlusion, LAD blood flow were increased compared to the baseline of both groups. However, there was no difference between groups in the LAD blood flow. The LMP after LAD reperfusion did not recover to the baseline level until 30 min after LAD reperfusion in control group (74%, 52% and 70% at 10, 20 and 30 min after LAD reperfusion, respectively). In nicardipine group, however, the LMP recovered to the baseline level at 20 min (99%), and increased more than the baseline level at 30 min (141%) after LAD reperfusion. Our findings suggest that the nicardipine augments the LMP following the release of a coronary occlusion.

Sex hormone modulation of serotonin-induced coronary vasodilation in isolated heart

The present study was designed to evaluate the differences in the coronary vasodilator actions of serotonin (5-HT) in isolated heart obtained from naive or castrated male and female rats that were treated with either estrogen or testosterone. Hearts from 12 groups of rats were used: male and female naive animals, castrated, castrated and treated with 17ß-estradiol (0.5 æg kg-1 day-1) for 7 or 30 days, and castrated and treated with testosterone (0.5 mg kg-1 day-1) for 7 or 30 days. After treatment, the vascular reactivity of the coronary bed was evaluated. Baseline coronary perfusion pressure (CPP) was determined and dose-response curves to 5-HT were generated. Baseline CPP differed between male (70 Ý 6 mmHg, N = 10) and female (115 Ý 6 mmHg, N = 12) naive rats. Maximal 5-HT-induced coronary vasodilation was higher (P<0.05) in naive female than in naive male rats. In both sexes, 5-HT produced endothelium-dependent coronary vasodilation. After castration, there was no significant difference in baseline CPP between hearts obtained from male and female rats (75 Ý 7 mmHg, N = 8, and 83 Ý 5 mmHg, N = 8, respectively). Castration reduced the 5-HT-induced maximal vasodilation in female and male rats (P<0.05). Estrogen treatment of castrated female rats restored (P<0.05) the vascular reactivity. In castrated male rats, 30 days of estrogen treatment increased (P<0.05) the responsiveness to 5-HT. The endothelium-dependent coronary vasodilator actions of 5-HT are greater in female rats and are modulated by estrogen. A knowledge of the mechanism of action of estrogen on coronary arteries could aid in the development of new therapeutic strategies and potentially decrease the incidence of cardiovascular disease in both sexes

The effects of vasopressin in isolated rat hearts.

The roles of cGMP, prostaglandins, the entry of extracellular Ca2+ through slow channels, endothelium and V1 receptors in the negative inotropic, chronotropic and coronary vasoconstrictor responses to arginine vasopressin (AVP) have been investigated in isolated perfused rat hearts. The bolus injection of 5 x 10(-5) M AVP produced a significant decrease in contractile force, heart rate and coronary flow. AVP also significantly decreased contractile force, heart rate and coronary flow in hearts pretreated with an inhibitor of soluble guanylate cyclase methylene blue (10(-6) M), an effective drug for removing endothelium saponin (500 micrograms/ml), an inhibitor of cyclooxygenase indomethacin (10(-5) M) or a calcium channel antagonist verapamil (5 x 10(-7) M). The potent V1 receptor antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (9 x 10(-5) M) did not alter effects of AVP but the very potent V1 receptor antagonist [beta-Mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin (8 x 10(-5) M) abolished these effects. Our results suggest that AVP produces negative inotropic, chronotropic and coronary vasoconstrictor effects in isolated perfused rat hearts. cGMP, prostaglandin release and Ca2+ entry does not involve in the effects of AVP. These effects are endothelium independent and mediated by V1 receptors. The use of V1 receptor antagonist [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin may be beneficial for preventing the negative inotropy, chronotropy and coronary vasoconstriction induced by AVP.

Vasopressina e morte encefálica / Vasopressin and brain death

A morte encefálica (ME) resulta numa perda completa dos mecanismos centrais de regulação da estabilidade hemodinâmica mesmo em pacientes com suporte adequado da ventilação, correção hidroeletrolítica e ácido-básica e suporte farmacológico convencional máximo da circulação. Acredita-se que a diminuição da vasopressina circulante influencia de maneira preponderante a estabilidade cardiocirculatória de pacientes com ME, sendo a sua administração exógena defendida por alguns autores no manuseio do potencial doador de órgãos. O artigo analisa e discute alguns estudos experimentais e clínicos relevantes em relação ao comportamento da vasopressina na ME e seu papel na manutenção da estabilidade cardiocirculatória, bem como sua potencial utilidade no manuseio destes pacientes. Desta análise concluímos que o comportamento da vasopressina na ME e o seu real valor na manutenção do potencial doador ainda não estão totalmente esclarecidos, necessitando de investigações futuras.