Fate of concomitant tricuspid regurgitation in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Owing to a lack of supportive data, tricuspid regurgitation (TR) is usually not addressed in patients undergoing coronary artery bypass grafting (CABG). Here we evaluated changes in TR degrees over time and its impact on survival in patients undergoing CABG. METHODS: We reviewed the data of 9726 patients who underwent isolated CABG between January 2000 and January 2021. According to preoperative TR severity, patients were stratified into nonsignificant (none to trivial, mild) and significant (moderate to severe) TR groups. We excluded patients who had undergone previous tricuspid valve surgery, pacemaker placement, and concomitant valve or ablative surgery. Propensity score matching and Cox proportional hazards models were used to identify associations between TR grade and the primary outcome of all-cause mortality. The secondary outcome was change in TR severity on the last echocardiogram. RESULTS: After propensity score matching, 380 patients in each group were identified. At baseline, 359 patients had moderate TR (94.5%) and 21 (5.5%) had severe TR. On the last follow-up echocardiogram, TR had improved in 40.5% of the patients in the significant TR group. Kaplan-Meier survival curves showed significantly lower survival in patients with significant preoperative TR compared to those with nonsignificant TR (P < .001). After adjusting for other confounders, survival was no worse in the patients with significant TR group (hazard ratio, 1.05; 95% confidence interval, 0.80-1.38; P = .70). CONCLUSIONS: Significant preoperative TR improved in 40.5% of patients after isolated CABG. After adjusting for other factors, significant TR did not affect long-term survival.

Appropriate patient selection or health care rationing? Lessons from surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves I trial.

OBJECTIVES: The study objectives were to (1) compare the safety of high-risk surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves (PARTNER) I trial with Society of Thoracic Surgeons national benchmarks; (2) reference intermediate-term survival to that of the US population; and (3) identify subsets of patients for whom aortic valve replacement may be futile, with no survival benefit compared with therapy without aortic valve replacement. METHODS: From May 2007 to October 2009, 699 patients with high surgical risk, aged 84 ± 6.3 years, were randomized in PARTNER-IA; 313 patients underwent surgical aortic valve replacement. Median follow-up was 2.8 years. Survival for therapy without aortic valve replacement used 181 PARTNER-IB patients. RESULTS: Operative mortality was 10.5% (expected 9.3%), stroke 2.6% (expected 3.5%), renal failure 5.8% (expected 12%), sternal wound infection 0.64% (expected 0.33%), and prolonged length of stay 26% (expected 18%). However, calibration of observed events in this relatively small sample was poor. Survival at 1, 2, 3, and 4 years was 75%, 68%, 57%, and 44%, respectively, lower than 90%, 81%, 73%, and 65%, respectively, in the US population, but higher than 53%, 32%, 21%, and 14%, respectively, in patients without aortic valve replacement. Risk factors for death included smaller body mass index, lower albumin, history of cancer, and prosthesis-patient mismatch. Within this high-risk aortic valve replacement group, only the 8% of patients with the poorest risk profiles had estimated 1-year survival less than that of similar patients treated without aortic valve replacement. CONCLUSIONS: PARTNER selection criteria for surgical aortic valve replacement, with a few caveats, may be more appropriate, realistic indications for surgery than those of the past, reflecting contemporary surgical management of severe aortic stenosis in high-risk patients at experienced sites.

Adaptation of bioassay to detect endothelium-derived relaxing factors from the canine atrial endocardium.

OBJECTIVE: The aim of this study was to assess the release of endothelium-derived relaxing factors from the endocardium of canine atrial appendage. METHODS: To study the release of endothelium-derived relaxing factor (EDRF) from intact atrial endocardial endothelium, tube-shaped sutures of canine atrial appendages were performed and effluents from these tubes were bioassayed (isolated perfused organ chamber system) for detection of EDRF in canine coronary artery. RESULTS: Effluent from the right atrial appendage caused a relaxation of 58.4 +/- 10.1% and the left atrial appendage 74.9 +/- 8.5% from the initial prostagladin F2alpha contraction in coronary artery. No significant statistical difference was detected in effluent from the right and left atrial appendages. This relaxation was abolished by treating the heart tubes with Triton X-100 and reduced by treatment with LNMMA, a competitive inhibitor of nitric oxide and with indomethacin, an inhibitor of the cyclo-oxygenase pathway, also indicating the release of vasodilatory prostanoids from the endocardial endothelium. CONCLUSION: This study showed for the first time, in vitro luminal release of EDRF and prostacyclin from the canine heart atrium. The ability of the endocardial endothelium to produce these factors could play an important role in preventing thrombus formation in the cardiac chambers.

Adaptação de um sistema de ensaio biológico para detecção de fatores relaxantes endoteliais derivados do endocárdio atrial canino / Adaptation of bioassay to detect endothelium-derived relaxing factors from the canine atrial endocardium

OBJETIVO: Estudar a liberação de fatores relaxantes derivados do endotélio (EDRF) pelo endocárdio de aurículas de corações caninos. MÉTODOS: Aurículas atriais caninas foram suturadas em forma de tubos e o efluente desses tubos foram submetidos a ensaios biológicos (sistema de perfusão isolada em câmaras de órgãos) utilizando artéria coronária canina, para a detecção de EDRFs. RESULTADOS: O efluente da aurícula direita promoveu relaxamento de 58,4 + 10,1 por cento e da aurícula esquerda 74,9 + 8,5 por cento da contração inicial obtida pela ação da prostagladina F2α em artéria coronária. Não houve diferença estatística no relaxamento da artéria coronária induzido pelos efluentes das aurículas direita e esquerda. O relaxamento induzido pelos efluentes das aurículas direita e esquerda foi abolido pelo tratamento das mesmas com Triton X-100. O tratamento das aurículas com L-NMMA, um inibidor competitivo da síntese de óxido nítrico, e com indometacina, um inibidor da via da ciclooxigenase, promoveu redução no relaxamento da artéria coronária induzido pelo efluente auricular, indicando que o endotélio endocárdico libera óxido nítrico e prostanóides. CONCLUSÕES: Esse estudo demonstra, pela primeira vez, a liberação luminal in vitro de EDRF e prostaciclina pelo átrio de coração canino. A habilidade do endotélio endocárdico em produzir esses fatores pode ter um papel importante na prevenção da formação de trombos nas câmaras cardíacas.

OBJECTIVE: The aim of this study was to assess the release of endothelium-derived relaxing factors from the endocardium of canine atrial appendage. METHODS: To study the release of endothelium-derived relaxing factor (EDRF) from intact atrial endocardial endothelium, tube-shaped sutures of canine atrial appendages were performed and effluents from these tubes were bioassayed (isolated perfused organ chamber system) for detection of EDRF in canine coronary artery. RESULTS: Effluent from the right atrial appendage caused a relaxation of 58.4 + 10.1 percent and the left atrial appendage 74.9 + 8.5 percent from the initial prostagladin F2α contraction in coronary artery. No significant statistical difference was detected in effluent from the right and left atrial appendages. This relaxation was abolished by treating the heart tubes with Triton X-100 and reduced by treatment with LNMMA, a competitive inhibitor of nitric oxide and with indomethacin, an inhibitor of the cyclo-oxygenase pathway, also indicating the release of vasodilatory prostanoids from the endocardial endothelium. CONCLUSION: This study showed for the first time, in vitro luminal release of EDRF and prostacyclin from the canine heart atrium. The ability of the endocardial endothelium to produce these factors could play an important role in preventing thrombus formation in the cardiac chambers.

Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate.

Segments of the canine internal mammary artery (35 mm in length) were suspended in vitro in an organ chamber containing physiological salt solution (95% O2/5% CO2, pH = 7.4, 37 degrees C). Segments were individually cannulated and perfused at 5 ml/minute using a roller pump. Vasorelaxant activity of the effluent from the perfused internal mammary arteries was bioassayed by measuring the decrease in tension induced by the effluent of the coronary artery endothelium-free ring which had been contracted with prostaglandin F2alpha (2 x 10(-6) M). Intraluminal perfusion of adenosine diphosphate (10(-5) M) induced significant increase in relaxant activity in the effluent from the perfused blood vessel. However, when adenosine diphosphate (10(-5) M) was added extraluminally to the internal mammary artery, no change in relaxant activity in the effluent was noted. In contrast, acetylcholine produced significant increase in the relaxant activity on the effluent of the perfused internal mammary artery with both intraluminal and extraluminal perfusion. The intraluminal and extraluminal release of endothelium-derived relaxing factor (EDRF) by acetylcholine (10(-5) M) can be inhibited by site-specific administration of atropine (10(-5) M). These experiments indicate that certain agonists can induce the release of EDRF only by binding to intravascular receptors while other agonists can induce endothelium-dependent vasodilatation by acting on neural side receptors.

Initial experience with dual antiplatelet thromboprophylaxis using clopidogrel and aspirin in patients with mechanical aortic prostheses.

BACKGROUND AND AIM OF THE STUDY: The aortic mechanical prosthesis (AMP) generates shear stress and causes erythrocyte fragmentation with ADP release that leads to platelet activation, the cause of thromboembolism. Thromboprophylaxis with the antiplatelet agents clopidogrel and aspirin (Clop-ASA) should reduce thromboembolic events in patients receiving an AMP. METHODS: Over an eight-year period at the authors' institutions, a total of 135 patients underwent aortic valve replacement (AVR), with or without concomitant thoracic aortic procedures, and received Clop-ASA as thromboprophylaxis. Platelet reactivity was measured using the Verify Now system. Thromboelastography was commenced in August 2006, and patients were followed at six-month intervals, with echocardiography and assessment of platelet reactivity. RESULTS: The total follow up was 4,776 months (equivalent to 398 patient-years (pt-yr)); the average follow up was 35.4 +/- 25 months. During follow up, 18 patients (13.3%) died, eight from coronary artery disease and three from valve-related causes. Five patients (3.7%; 1.2%/pt-yr) had bleeding complications, but none experienced valve thrombosis. Two patients (1.5%; 0.5%/pt-yr) had a transient ischemic attack (TIA); one of these occurred in a patient who discontinued Clop-ASA, and the other in a responder to Clop-ASA. Seven patients (5.2%; 1.7%/pt-yr) had strokes, one of which occurred at 48.5 months after AVR. Of the remaining six patients who had a stroke, one was a non-responder to clopidogrel and five had stopped taking Clop-ASA. The incidence of strokes before using the Accumetrics and TEG devices was 2.5% per pt-yr, but only 1.0% per pt-yr thereafter. CONCLUSION: Thromboprophylaxis in patients with AMP receiving Clop-ASA seems to be effective. Patients had a low incidence of bleeding, TIA and ischemic stroke, and no valve thrombosis. The use of assays to determine platelet reactivity helped to identify those patients who were resistant to clopidogrel, hyporesponders, and poorly compliant patients. Notably, the incidence of strokes after implementing assays to monitor platelet reactivity was reduced. Deaths were due primarily to myocardial infarction, and none of the deaths was anticoagulant-related. Patients receiving Clop-ASA should undergo routine testing of platelet reactivity, and also continue antiplatelet therapy so as to reduce the risk of ischemic stroke.

High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries.

OBJECTIVE: Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. METHODS: To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. RESULTS: Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10(-9)-10(-4) M), Ach (10(-9)-10(-4) M) and NaF (0.5-9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10(-9)-10(-5) M) or SNP (10(-9)-10(-6) M) was unaltered following exposure to either low or high ultrasonic energy outputs. CONCLUSION: These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.

Ondas ultra-sônicas de alta freqüência causam disfunção endotelial em artérias coronárias caninas epicárdicas / High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries

OBJETIVO: Aplicação de energia por ultra-som pode facilitar a remoção da placa ateromatosa, mas o efeito desse procedimento em vasos próximos ainda é matéria de estudos experimentais. MÉTODOS: Para determinar se a energia ultra-sônica compromete a produção de óxido nítrico, segmentos de artérias coronárias caninas foram expostos a baixos (0-10 W) e altos (25 W) níveis de energia por 15 segundos, utilizando-se protótipo de aparelho para a realização de endarterectomia. Após exposição, segmentos das artérias coronarianas foram estudados em organ chambers. Para os ensaios farmacológicos foram utilizadas as seguintes drogas:difosfato de adenosina (ADP), acetilcolina (Ach) e fluoreto de sódio (NaF) para a avaliação do relaxamento dependente do endotélio. O nitroprussiato de sódio (NPS) e o isoproterenol foram utilizados para a avaliação do relaxamento independente do endotélio. RESULTADOS: A aplicação de alta energia ultra-sônica comprometeu o relaxamento dependente do endotélio induzido por ADP (10-9 - 10-4 M), Ach (10-9 - 10-4 M) e NaF (0,5 -9,5 mM) em artérias coronarianas epicárdicas. Entretanto, baixos valores de energia ultra-sônica não alteraram o relaxamento dependente do endotélio (nem o relaxamento máximo e nem a EC50) induzido pelos mesmos agonistas. O relaxamento da musculatura lisa vascular induzido por isoproterenol (10-9 - 10-5 M) ou NPS (10-9 - 10-6 M) não foi comprometido, tanto por baixos, quanto por altos níveis de energia ultra-sônica. CONCLUSÃO: Os experimentos demonstram que altas energias ultra-sônicas alteram a função endotelial. Entretanto, o ultra-som não altera a habilidade de relaxamento da musculatura lisa vascular de artérias caninas epicárdicas.

OBJECTIVE: Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. METHODS: To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. RESULTS: Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10-9 - 10-4 M), Ach (10-9 - 10-4 M) and NaF (0.5 - 9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10-9 - 10-5 M) or SNP (10-9 - 10-6 M) was unaltered following exposure to either low or high ultrasonic energy outputs. CONCLUSION: These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.

Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia.

Nitric oxide and prostacyclin are endogenous endothelium-derived vasodilators, but little information is available on their release during hypothermia. This study was carried out to test the hypothesis that endothelium may modulate vascular reactivity to decreased temperature changes. Segments of contracted (prostaglandin F(2alpha), 2x10(-6)M) canine coronary, femoral, and renal arteries, with and without endothelium, were in vitro ("organ chambers") exposed to progressive hypothermia (from 37 to 10 degrees C) in graded steps. The study is limited to physiological measurements of vascular tone, in the presence or absence of PGI(2) and/or NOS inhibitors, which show correlation with the relaxation. Hypothermia induced vasodilatation of vessels with intact endothelium, which became endothelium-independent below 20 degrees C. This vasodilatation began at 35 degrees C and, in the presence of indomethacin (2x10(-6)M), at 30 degrees C. Endothelium-dependent vasodilatation to hypothermia was blocked by L-NMMA or L-NOARG (10(-5)M), two competitive inhibitors of nitric oxide synthase (n=5 each, P<0.05). Oxyhemoglobin (2x10(-6)M) also inhibited vasodilatation induced by hypothermia (n=6, P<0.05). Pretreatment with either atropine or pirenzepine (10(-6)M) inhibited hypothermia-mediated vasodilatation (n=5 each, P<0.05). The present in vitro study concluded that the endothelium is sensitive to temperature variations and indicated that PGI(2) and NO-dependent pathways may be involved endothelium-dependent relaxation to hypothermia. The endothelium-dependent vasodilatation to hypothermia, in systemic and coronary arteries, is mediated by the M1 muscarinic receptor.

[Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries]. / Amiodarona causa vasodilatação dependente do endotélio em artérias coronárias caninas.

OBJECTIVE: To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water. METHODS: Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of polysorbate 80, amiodarone dissolved in water, amiodarone dissolved in polysorbate 80, and a commercial presentation of amiodarone (Cordarone). The experiments were conducted in the presence of the following enzymatic blockers: only indomethacin, Nomega-nitro-L-arginine associated with indomethacin, and only Nomega-nitro-L-arginine. RESULTS: Polysorbate 80 caused a small degree of nonendothelium-dependent relaxation. Cordarone, amiodarone dissolved in water, and amiodarone dissolved in polysorbate 80 caused endothelium-dependent relaxation, which was greater for amiodarone dissolved in polysorbate and for Cordarone. Only the association of indomethacin and Nomega-nitro-L-arginine could eliminate the endothelium-dependent relaxation caused by amiodarone dissolved in polysorbate 80. CONCLUSION: The results obtained indicate that vasodilation promoted by amiodarone in canine coronary arteries is mainly caused by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.

Amiodarona causa vasodilatação dependente do endotélio em artérias coronárias caninas / Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries

OBJETIVO: Avaliar os efeitos vasodilatadores da amiodarona em artérias coronárias caninas empregando soluções de amiodarona dissolvida em polisorbato 80 ou em água. MÉTODOS: Anéis de artéria coronária, com e sem o endotélio íntegro, foram imersos em solução de krebs e conectadas a um transdutor para aferição de força isométrica promovida por contração vascular. As artérias foram expostas a concentrações crescentes de polisorbato 80, amiodarona dissolvida em água, amiodarona dissolvida em polisorbato 80 e uma apresentação comercial da amiodarona (Cordarone®). Os experimentos foram conduzidos na presença e na ausência dos seguintes bloqueadores enzimáticos: apenas indometacina, Nω-nitro-L-arginina associada à indometacina e apenas Nω-nitro-L-arginina. RESULTADOS: O polisorbato 80 causou pequeno relaxamento não dependente do endotélio. O Cordarone®, a amiodarona dissolvida em água e em polisorbato 80 promoveram relaxamento dependente do endotélio, que foi de maior magnitude para a amiodarona dissolvida em polisorbato e para o Cordarone®. Apenas a associação de indometacina com a Nω-nitro-L-arginina foi capaz de abolir o relaxamento dependente do endotélio provocado pela amiodarona dissolvida em polisorbato 80. CONCLUSAO: Os resultados obtidos indicam que a vasodilatação promovida pela amiodarona em artérias coronárias caninas é causada principalmente pela estimulação da liberação de óxido nítrico e fatores endoteliais relaxantes dependentes das ciclo-oxigenases.

Endothelium-dependent relaxation in response to poly-L-arginine in canine coronary arteries: implications about hyperpolarization as a mechanism of vasodilatation.

OBJECTIVE: To study the mechanism by which poly-L-arginine mediates endothelium-dependent relaxation. METHODS: Vascular segments with and without endothelium were suspended in organ chambers filled with control solution maintained at 37 C and bubbled with 95% O2 / 5% CO2. Used drugs: indomethacin, acetycholine, EGTA, glybenclamide, ouabain, poly-L-arginine, methylene blue, N G-nitro-L-arginine, and verapamil and N G-monomethyl-L-arginine. Prostaglandin F2 and potassium chloride were used to contract the vascular rings. RESULTS: Poly-L-arginine (10-11 to 10-7 M) induced concentration-dependent relaxation in coronary artery segments with endothelium. The relaxation to poly-L-arginine was attenuated by ouabain, but was unaffected by glybenclamide. L-NOARG and oxyhemoglobin caused attenuation, but did not abolish this relaxation. Also, the relaxations was unaffected by methylene blue, verapamil, or the presence of a calcium-free bathing medium. The endothelium-dependent to poly-L-arginine relaxation was abolished only in vessels contracted with potassium chloride (40 mM) in the presence of L-NOARG and indomethacin. CONCLUSION: These experiments indicate that poly-L-arginine induces relaxation independent of nitric oxide.

Effect of arginine vasopressin on the canine epicardial coronary artery: experiments on V1-receptor-mediated production of nitric oxide.

OBJECTIVE: To determine whether arginine vasopressin releases endothelium-derived nitric oxide (EDNO) from the epicardial coronary artery. METHODS: We studied segments of canine left circumflex coronary arteries suspended in organ chambers to measure isometric force. The coronary artery segments were contracted with prostaglandin F2alpha (2 x 10-6M) and exposed to a unique, strong arginine vasopressin concentration (10-6M) or titrated concentrations (10-9 a 10-5 M). RESULTS: The unique dose of arginine vasopressin concentration (10-6M) induced transient, but significant (p<0.05), relaxation in arterial segments with endothelium, and an increase, not significant, in tension in arteries without endothelium. Endothelium-dependent relaxation to arginine vasopressin was inhibited by Ng-monomethyl-L-arginine (L-NMMA, 10-5M) or N G-nitro-L-arginine (L-NOARG) (10-4M), 2 inhibitors of nitric oxide synthesis from L-arginine. Exogenous L-arginine (10-4M), but not D-arginine (10-4M), reversed the inhibitory effect of L-NMMA on vasopressin-mediated vasorelaxation. Endothelium dependent relaxation to vasopressin was also reversibly inhibited by the vasopressin V1-receptor blocker d(CH2)5Try(Me) arginine vasopressin (10-6M) (n=6, P<0.05). CONCLUSION: Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide release from L-arginine.

Relaxamento dependente do endotélio causado pela Poli-L-Arginia. Implicações sobre a hiperpolarizaçäo como mecanismo de vasodilataçäo / Endothelium-dependent relaxation in response to poly-L-arginine in canine coronary arteries: implications about hyperpolarization as a mechanism of vasodilatation

OBJECTIVE: To study the mechanism by which poly-L-arginine mediates endothelium-dependent relaxation. METHODS: Vascular segments with and without endothelium were suspended in organ chambers filled with control solution maintained at 37ºC and bubbled with 95 percent O2 / 5 percent CO2. Used drugs: indomethacin, acetycholine, EGTA, glybenclamide, ouabain, poly-L-arginine, methylene blue, N G-nitro-L-arginine, and verapamil and N G-monomethyl-L-arginine. Prostaglandin F2á and potassium chloride were used to contract the vascular rings. RESULTS: Poly-L-arginine (10-11 to 10-7 M) induced concentration-dependent relaxation in coronary artery segments with endothelium. The relaxation to poly-L-arginine was attenuated by ouabain, but was unaffected by glybenclamide. L-NOARG and oxyhemoglobin caused attenuation, but did not abolish this relaxation. Also, the relaxations was unaffected by methylene blue, verapamil, or the presence of a calcium-free bathing medium. The endothelium-dependent to poly-L-arginine relaxation was abolished only in vessels contracted with potassium chloride (40 mM) in the presence of L-NOARG and indomethacin. CONCLUSION: These experiments indicate that poly-L-arginine induces relaxation independent of nitric oxide

Efeito da vasopressina em artérias coronárias epicárdicas caninas. Experimentos sobre a produção de óxido nítrico mediante a estimulação de receptores V1 / Effect of arginine vasopressin on the canine epicardial coronary artery. Experiments on V1-receptor-mediated production of nitric oxide

OBJECTIVE: To determine whether arginine vasopressin releases endothelium-derived nitric oxide (EDNO) from the epicardial coronary artery. METHODS: We studied segments of canine left circumflex coronary arteries suspended in organ chambers to measure isometric force. The coronary artery segments were contracted with prostaglandin F2alpha (2 x 10-6M) and exposed to a unique, strong arginine vasopressin concentration (10-6M) or titrated concentrations (10-9 a 10-5 M). RESULTS: The unique dose of arginine vasopressin concentration (10-6M) induced transient, but significant (p<0.05), relaxation in arterial segments with endothelium, and an increase, not significant, in tension in arteries without endothelium. Endothelium-dependent relaxation to arginine vasopressin was inhibited by Ng-monomethyl-L-arginine (L-NMMA, 10-5M) or N G-nitro-L-arginine (L-NOARG) (10-4M), 2 inhibitors of nitric oxide synthesis from L-arginine. Exogenous L-arginine (10-4M), but not D-arginine (10-4M), reversed the inhibitory effect of L-NMMA on vasopressin-mediated vasorelaxation. Endothelium dependent relaxation to vasopressin was also reversibly inhibited by the vasopressin V1-receptor blocker d(CH2)5Try(Me) arginine vasopressin (10-6M) (n=6, P<0.05). CONCLUSION: Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide release from L-arginine

Reatividade vascular da artéria mamária interna: estudos farmacológicos comparativos entre artérias caninas direita e esquerda / Vascular reactivity of the internal mammary artery: comparative pharmacological studies between canine right and left arteries

Para estudos comparativos da reatividade vascular entre artéria mamária interna (AMI) canina direita e esquerda, realizaram-se experimentos "in vitro" utilizando-se banhos orgânicos ("organ chambers") e ensaios biológicos: 1) os produtos plaquetários ADP e 5-HT induziram, respectivamente, vasodilatação dependente e independente do endotélio; 2) os autacóides, bradicinina e histamina, também induziram vasodilatação, respectivamente, dependente e independente do endotélio; 3) o A23187, vasodilatador independente de receptor, induziu relaxamentos dependentes do endotélio; 4) dopamina, dobutamina, papaverina e a poli-L-arginina induziram vasodilatações independentes do endotélio; 5) a NOR induziu intensa vasoconstrição comparável à causada pelo KCI e pela endotelina; 6) em 83 porcento de 24 ensaios, a liberação basal de NO foi maior na AMI esquerda, em comparação com a AMI direita; 7) ensaios biológicos de AMIs demonstraram a importância da PGI2 nas condições de hipóxia, uma vez que a indometacina aboliu vasodilatação adicional em resposta à hipóxia em condições de vasodilatação induzida pela liberação basal de NO; 8) não ocorreram diferenças significantes de resposta, comparando-se estudos realizados em AMIs direita e esquerda

Efeito protetor da criocardioplegia cristalóide na isquemia global e reperfusäo durante circulaçäo extracorpórea: um mecanismo dependente do endotélio? / Protective effect of crystalloid cryocardioplegia in the global ischemia and reperfusion during extracorporeal circulation: an endothelium-dependent mechanism?

Estudos prévios demonstraram que o comprometimento da produçäo de EDRF/NO mediada por receptores, após isquemia global e reperfusäo, possa ser devido a uma disfunçäo de G-proteínas que liga os receptores da célula endotelial à via da síntese de EDRF/NO. O presente trabalho experimental sugere que a criocardioplegia cristalóide, associada a hipotermia tópica, previne ou pode reverter, em parte, a disfunçäo endotelial nas mesmas condiçöes. Mais estudos seräo necessários para conclusöes mais definitivas, pois as análises estatísticas mais acuradas sugeriram aumento da amostragem. Este detalhe talvez seja devido às grandes dificuldades de uniformizaçäo relacionada a este tipo de experimentos. Além disso, demonstrou-se pela primeira vez que a hipotermia, por si só, pode estimular a liberaçäo de EDRF/NO pelo endotélio vascular. Isto sugere que o endotélio possa ser um importante sensor de mudanças da temperatura sangüínea e tem importantes implicaçöes para o entendimento da fisiologia da CEC e dos mecanismos locais de auto-regulaçäo.

Cardioplegia cristalóide, barotrauma e funçäo endotelial: consideraçöes experimentais / Crystalloid cardioplegia, barotrauma and endothelium function: experimental considerations

O presente ensaio experimental estudou o efeito da infusao de soluçao cardioplégica cristalóide a altas pressoes sobre a funçao endotelial de artérias epicárdicas de caes. Nao se encontraram alteraçoes a nível de receptores (curvas dose-respostas à ACH e ADP; da transduçao do sinal iniciado nos receptores/sitema de G-proteínas (fluoreto de sódio) e nos processos intracelulares da produçao de EDRF/NO (fosfolipase C e ionóforo do cálcio A23187). A funçao da musculatura lisa vascular nao foi afetada quando se analisaram as respostas relaxantes (nitroprussiato de sódio e isoproterenol) e contráteis (KCI e prostaglandina 2alfa). Estes achados permitem as seguintes consideraçoes especulativas: a) O barotrauma produzido pela infusao da cardioplegia cristalóide a altas pressoes ocorreria apenas em circulaçoes coronarianas previamente doentes? b) Uma vez que as infusoes duraram de 2 a 3 minutos, seria o barotrauma coronariano um fenômeno dependente do tempo de infusao? c) Para que ocorra o barotrauma seriam necessários níveis mais elevados de Potássio? d) Questionara existência do fenômeno do barotrauma coronariano produzido pela infusao de soluçoes cadioplégicas pelo menos nas condiçoes experimentais utilizadas. e) A metodologia empregada estuda apenas as reatividades vasculares de artérias coronarias epicárdicas. estas artérias seriam menos sensíveis aos efeitos da pressao de infusao da cardioplegia do que a microcirculaçao coronariana? f) Seria a circulaçao coronária do cao menos sensível a altas pressoes do que do homem? Estas observaçoes experimentais sugerem que a infusao de cardioplegia cristalóide, moderadamente hipocalêmica, a altas pressoes em um tempo de 2 a 3 minutos, nao interfere com a produçao de EDRF/NO pelo endotélio de coronárias epicárdicas do cao.