Coronary collateral flow: effect of drugs and perfusion pressure

Summary In 35 mongrel dogs acute myocardial infarction was produced by ligating the anterior descending branch of the left coronary artery and subsequent embolization of the peripheral area of the descending branch with microspheres. Retrograde flow and coronary retrograde pressure were measured before and after embolization as well as after embolization before and during the action of coronary dilating drugs. After embolization, the mean retrograde flow represented the whole coronary collateral flow, and the retrograde pressure equalled the true coronary collateral perfusion pressure. Following embolization, the mean retrograde pressure significantly increased from 20±2 to 69±3 mm Hg, i.e. to 73% of the mean aortic pressure. There was a simultaneous rise in retrograde flow from 3.99±0.78 to 6.19±1.16 ml/(min · 100 g), i.e. 12% of the antegrade perfusion. A significant correlation between coronary collateral flow and collateral perfusion pressure could be demonstrated. The average increase in collateral flow was 1.14 ml/(min · 100 g), i.e. 21 %, when the perfusion pressure rose from 70 to 80 mm Hg.After drug infusions, a slight increase in coronary collateral flow was observed, provided that the perfusion pressure remained unchanged. This increase was significant after nitroglycerine (+ 13±3 %) and after papaverine (+ 11±5%). When the perfusion pressure decreased, there was a decrease in collateral flow. When, however, under isoproterenol the decreased perfusion pressure was brought back to control level my means of a blood infusion, the collateral flow also increased and was then slightly, but significantly, above control (+ 4%).It can be concluded that, provided the perfusion pressure remains constant, the application of coronary dilating drugs can slightly improve the coronary collateral flow. This small effect might be of vital importance for the treatment of myocardial infarction. Myocardial steal only appeared when the perfusion pressure decreased.

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Über den Einfluß von Pharmaka und des Perfusionsdruckes auf die Kollateraldurchblutung des Herzens

Zusammenfassung Bei 35 narkotisierten Hunden wurde der Ramus descendens der linken Koronararterie akut unterbunden und das zugehörige Stromgebiet mit Latexpartikeln embolisiert. Der retrograde Fluß und der retrograde Druck wurden vor und nach Embolisation sowie nach der Embolisation vor und während des Einflusses von Koronardilatatoren gemessen. Der retrograde Fluß nach Mikroembolisation entspricht dem wahren Kollateralfluß und der retrograde Druck dem wahren Perfusionsdruck der Kollateralgefäße. Nach Mikroembolisation stieg der retrograde Druck signifikant von 20±2 auf 69±3 mm Hg, das entspricht 73% des mittleren Aortendruckes. Gleichzeitig stieg der retrograde Fluß von 3,99±0,78 auf 6,19±1,16 ml/(min · 100 g), das sind 12% der antegraden Durchblutung. Der durchschnittliche Anstieg der Kollateraldurchblutung betrug 1,14 ml/(min. · 100 g), das sind + 21%, bei einer Zunahme des Perfusionsdruckes von 70 auf 80 mm Hg.Unter der Applikation von Koronardilatatoren konnte ein geringer Anstieg der Kollateraldurchblutung beobachtet werden, vorausgesetzt, daß der Perfusionsdruck unverändert blieb. Dieser Anstieg war unter Nitroglycerin, (+ 13 ±3%) und unter Papaverin (+11±5%) signifikant. Die Kollateraldurchblutung nahm ab, wenn der Perfusionsdruck unter dem Einfluß des Pharmakons abfiel. Wurde der unter Isoproterenol gesunkene Perfusionsdruck mittels Bluttransfusion wieder auf den Ausgangswert angehoben, so stieg die Kollateraldurchblutung wieder an und lag dann mit +4% gering, aber signifikant über dem Ausgangswert.Aufgrund dieser Befunde kann geschlossen werden, daß Koronardilatatoren die Kollateraldurchblutung geringgradig verbessern können unter der Voraussetzung, daß der Perfusionsdruck nicht absinkt. Dieser geringe pharmakologische Effekt könnte jedoch von entscheidender Bedeutung bei der Behandlung des Myokardinfarktes sein. Ein myocardial steal tritt nur bei einem Abfall des Perfusionsdruckes ein.

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With 2 figures and 3 tables

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Supported by a grant of the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 30, Kardiologie, Düsseldorf.     

Can ultrasound guidance reduce the risk of pneumothorax following thoracentesis?,

OBJECTIVE:

Thoracentesis is one of the bedside procedures most commonly associated with iatrogenic complications, particularly pneumothorax. Various risk factors for complications associated with thoracentesis have recently been identified, including an inexperienced operator; an inadequate or inexperienced support team; the lack of a standardized protocol; and the lack of ultrasound guidance. We sought to determine whether ultrasound-guided thoracentesis can reduce the risk of pneumothorax and improve outcomes (fewer procedures without fluid removal and greater volumes of fluid removed during the procedures). In our comparison of thoracentesis with and without ultrasound guidance, all procedures were performed by a team of expert pulmonologists, using the same standardized protocol in both conditions.

METHODS:

A total of 160 participants were randomly allocated to undergo thoracentesis with or without ultrasound guidance (n = 80 per group). The primary outcome was pneumothorax following thoracentesis. Secondary outcomes included the number of procedures without fluid removal and the volume of fluid drained during the procedure.

RESULTS:

Pneumothorax occurred in 1 of the 80 patients who underwent ultrasound-guided thoracentesis and in 10 of the 80 patients who underwent thoracentesis without ultrasound guidance, the difference being statistically significant (p = 0.009). Fluid was removed in 79 of the 80 procedures performed with ultrasound guidance and in 72 of the 80 procedures performed without it. The mean volume of fluid drained was larger during the former than during the latter (960 ± 500 mL vs. 770 ± 480 mL), the difference being statistically significant (p = 0.03).

CONCLUSIONS:

Ultrasound guidance increases the yield of thoracentesis and reduces the risk of post-procedure pneumothorax. (Chinese Clinical Trial Registry identifier: ChiCTR-TRC-12002174 [http://www.chictr.org/en/])     

Assessment of prenatal exposure to ethanol by meconium analysis: results of an Italian multicenter study

Background: This study estimated in 7 Italian cities the prevalence of prenatal exposure to ethanol by determining fatty acid ethyl esters (FAEEs; palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, and arachidonic esters) and ethyl glucuronide (EtG) in neonatal meconium samples. Methods: A total of 607 meconium samples were obtained from neonatal wards of 7 public hospitals: Verona and San Daniele del Friuli in the northeast of the country, Reggio Emilia in the middle east, Florence and Rome in the center, and Naples and Crotone in the southwest of the peninsula. Meconium biomarkers were assessed by a validated methodology using liquid chromatography–tandem mass spectrometry and the results categorized using the accepted cutoff of 2 nmol/g total amount of 7 FAEEs and 2 nmol/g EtG, to differentiate between heavy maternal ethanol use during pregnancy and occasional or no use at all. Results: On the basis of the above‐reported cutoffs, the overall prevalence of newborns prenatally exposed to maternal ethanol was 7.9%: 0% in Verona, 4.0% in San Daniele del Friuli, 4.9% in Naples, 5.0% in Florence, 6.2% in Crotone, up to 10.6% in Reggio Emilia, and 29.4% in Rome. Low maternal education level and younger maternal age were associated with biomarker scores over the cutoff. There was also a significant correlation between the highest percentage of prenatal exposure in the capital and certain maternal sociodemographic characteristics. Conclusions: These results indicate considerable variability in the prevalence of fetal exposure to ethanol in different Italian cities, as determined by the objective measurement of biomarkers in meconium. These data, together with previous ones obtained in Barcelona, Spain, indicate that gestational ethanol exposure is widespread, at least in parts of Europe.     

The mechanism of beta-adrenergic preconditioning: roles for adenosine and ROS during triggering and mediation

The aim of this study was to investigate the mechanism of beta-adrenergic preconditioning (BPC). The roles of adenosine and its receptor subtypes, the generation of oxygen free radicals (ROS) and activation of the K(ATP) channels as well as the phosphoinositide-3-kinase (PI(3)K)/PKB/Akt and extracellular signal-regulated kinase (ERK) signal transduction pathways during the triggering and mediation phases were evaluated. Using the isolated working rat heart, BPC was elicited by administration of denopamine (beta1 adrenergic receptor agonist, 10(-7)?M), isoproterenol (beta1/beta2 adrenergic receptor agonist, 10(-7)?M) or formoterol (beta2 adrenergic receptor agonist, 10(-9)?M) for 5?min followed by 5?min washout. Index ischaemia was 35?min regional ischaemia and infarct size determined using the tetrazolium method. The role of adenosine was studied using adenosine deaminase and selective antagonists as well as the PI(3)K and ERK inhibitors, wortmannin and PD98,059, bracketing the triggering and mediating phases. Involvement of ROS, PKC, the mitochondrial K(ATP) channels, release of endogenous opioids and bradykinin was studied by administration of N-acetyl cysteine (NAC), bisindolylmaleimide, the K(ATP) channel blocker 5-hydroxydecanoate (5-HD), naloxone or HOE140, respectively. Activation of PKB/Akt and ERKp44/p42 during triggering and reperfusion was determined by Western blot. Preconditioning with all three beta-adrenergic receptor agonists caused a reduction in infarct size and an improvement in postischaemic function. BPC preconditioning with isoproterenol, denopamine or formoterol was abolished by the adenosine A3 receptor antagonist MRS1191 during both the triggering and mediation phases. Isoproterenol-induced preconditioning (beta1/beta2 PC) was attenuated by MRS1754, an adenosine A(2B) receptor antagonist, during the triggering phase and abolished during reperfusion. The mediation phase of beta1/beta2 PC was also abolished by ZM241385, an adenosine A(2A) antagonist. The free radical scavenger NAC caused a significant attenuation of cardioprotection induced by isoproterenol when administered during both trigger and mediation phases, while being effective during the trigger phase with denopamine and during reperfusion in formoterol preconditioned hearts. The mitochondrial K(ATP) channel blocker, 5-HD, was without effect on beta1/beta2 PC during both triggering and mediation phases. BPC in rat hearts is dependent on activation of the A(3) adenosine receptors by endogenously produced adenosine and production of free radicals during the triggering and mediation phases while the A(2A) and A(2B) adenosine receptors participate mainly during reperfusion. The mitochondrial K(ATP) channels do not contribute to cardioprotection at any stage. Activation of ERK and PI3K/PKB/Akt during the triggering and reperfusion phases is associated with cardioprotection.     

Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram

Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using ¹²³I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects’ Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.     

New pharmacotherapy options for noninfectious posterior uveitis

International Ophthalmology - Noninfectious inflammation of the posterior eye segment represents an important cause of visual impairment. It often affects relatively young people and causes a...