RESUMO
Systemic factors and blood flow velocity related to atherosclerosis have been examined mainly separately or by in vitro studies. The aim of our study was to investigate the association between local coronary blood flow (corrected TIMI frame count, CTFC) and systemic atherosclerosis-related inflammatory parameters such as soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (Il-6), high sensitivity C-reactive protein (hsCRP) and von Willebrand factor (vWF) in humans. We enrolled the following groups of ischemic heart disease (IHD) patients: patients with coronary stenosis and stable (CAD, n = 96) or unstable angina (ACS, n = 27), patients with documented myocardial ischemia and normal coronary angiogram (NEG, n = 68). Patient groups showed only marginal differences in CTFC or sICAM-1 levels. In contrast, when IHD patients were studied individually, general positive correlation was found between CTFC and sICAM-1 level (r = 0.33; in NEG r = 0.25; in CAD r = 0.37; in ACS r = 0.61), being the strongest in ACS. The relation was independent from age, gender, BMI, smoking, hypertension, diabetes, previous myocardial infarction, family history of IHD, medication, hsCRP, IL-6 and vWF levels. (odds ratio, OR = 6.4; CI 95%: 2.43-16.84; p < 0.05). Nevertheless, correlation between CTFC and IL-6, hsCRP, vWF levels was not found. These results indicate inverse correlation between coronary blood flow and adhesion molecule production independently from conventional cardiovascular risk factors and inflammatory markers.
Assuntos
Molécula 1 de Adesão Intercelular/sangue , Isquemia Miocárdica/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Proteína C-Reativa/análise , Circulação Coronária/fisiologia , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fator de von Willebrand/análiseRESUMO
Nucleotides regulate various effects including vascular tone. This study was aimed to characterize P2Y receptors on endothelial cells of the aorta of C57BL6 mice. Five adjacent segments (width 2 mm) of the thoracic aorta were mounted in organ baths to measure isometric force development. Nucleotides evoked complete (adenosine 5' triphosphate (ATP), uridine 5' triphosphate (UTP), uridine 5' diphosphate (UDP); >90%) or partial (adenosine 5' diphosphate (ADP)) relaxation of phenylephrine precontracted thoracic aortic rings of C57BL6 mice. Relaxation was abolished by removal of the endothelium and was strongly suppressed (>90%) by inhibitors of nitric oxide synthesis. The rank order of potency was: UDP approximately UTP approximately ADP>adenosine 5'-[gamma-thio] triphosphate (ATPgammaS)>ATP, with respective pD2 values of 6.31, 6.24, 6.22, 5.82 and 5.40. These results are compatible with the presence of P2Y1 (ADP>ATP), P2Y2 or P2Y4 (ATP and UTP) and P2Y6 (UDP) receptors. P2Y4 receptors were not involved, since P2Y4-deficient mice displayed unaltered responses to ATP and UTP. The purinergic receptor antagonist suramin exerted surmountable antagonism for all agonists. Its apparent pKb for ATP (4.53+/-0.07) was compatible with literature, but the pKb for UTP (5.19+/-0.03) was significantly higher. This discrepancy suggests that UTP activates supplementary non-P2Y2 receptor subtype(s). Further, pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) showed surmountable (UTP, UDP), nonsurmountable (ADP) or no antagonism (ATP). Finally, 2'-deoxy-N6-methyladenosine3',5'-bisphosphate (MRS2179) inhibited ADP-evoked relaxation only. Taken together, these results point to the presence of functional P2Y1 (ADP), P2Y2 (ATP, UTP) and P2Y6 (UDP) receptors on murine aorta endothelial cells. The identity of the receptor(s) mediating the action of UTP is not fully clear and other P2Y subtypes might be involved in UTP-evoked vasodilatation.
Assuntos
Aorta Torácica/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Receptores Purinérgicos P2/efeitos dos fármacos , Animais , Aorta Torácica/citologia , Ligação Competitiva/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/citologia , Nucleotídeos/farmacologia , Agonistas do Receptor Purinérgico P2 , Antagonistas do Receptor Purinérgico P2 , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/fisiologia , Vasodilatadores/farmacologiaRESUMO
BACKGROUND: Verapamil is traditionally applied prophylactically in transradial procedures to prevent radial artery spasm. However, verapamil may have side effects and is contraindicated in some clinical settings. METHODS AND RESULTS: During an investigator-initiated, randomized, double-blind trial, we evaluated the need for preventive verapamil administration. After vascular access was established, patients received either 5 mg verapamil (n=297) or placebo (n=294). We compared the rate of access site conversions as primary end point using a superiority margin of 5%. Occurrence of code breaks (composite of conversions and unplanned use of verapamil), overall verapamil use, procedural and fluoroscopic times, contrast volume, and subjective pain were investigated as secondary end points. The rate of access site conversions was not different in the 2 arms (placebo 1.7% versus verapamil 0.7%, P=0.28, difference 1.0%, 95% CI for the difference -1.1% to 3.3%). Proportion of code breaks was similar in the 2 groups (3.4% versus 1.3%, P=0.11), whereas overall verapamil use was markedly lower in the placebo arm (2.0% versus 100%, P<0.0001). Procedural time (median [IQR] 16.0 minutes [9.0 to 30.0 minutes] versus 17.0 minutes [10.0 to 31.0 minutes], P=0.37), fluoroscopic time (4.4 minutes [2.1 to 9.6 minutes] versus 4.8 minutes [2.4 to 10.7 minutes], P=0.28), contrast volume (72.5 mL [48.0 to 146.0 mL] versus 75.5 mL [47.0 to 156.5 mL], P=0.74), and pain score (P for trend=0.12) were comparable in the 2 groups. CONCLUSIONS: The preventive use of verapamil may be unnecessary for transradial procedures. The omission of prophylactic verapamil may not only reduce the rate of potential complications related to the drug but also allow the safe extension of the transradial method to those with contraindications to verapamil. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01402427.