Injection Of Adenosine Research Articles

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire

BackgroundDoppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo.MethodsWe perfused glass pipes of defined inner diameters (1.5 – 5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes.ResultsIn vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r2 > 0.85). Above a critical Reynolds number of 500 – indicating turbulent flow – the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 ± 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments.ConclusionDoppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making.

The changes of fractional flow reserve after intracoronary nitrate and Nicorandil injection in coronary artery ectasia

Background and Objectives:Little data exist relating to the mechanism of myocardial ischemia in patients with coronary artery ectasia (CAE). The purpose of this study was to evaluate the fractional flow reserve (FFR), as an index of myocardial ischemia, in patients with CAE. Subjects and Methods:Ten patients (7 males, 54.0±12.6 years) who diagnosed as CAE, by coronary angiographies, between March 2002 and July 2002, were analyzed. The clinical diagnosis of all the patients was unstable angina. FFR were performed using a pressure wire on the patients diagnosed with slow flow CAE from their coronary angiograms. After measurement of the baseline FFR using adenosine 20 μg for the right coronary artery, and 24 μg for the left anterior descending artery, the changes in the FFR with 500 μg of intracoronary nitrate and 2 mg of Nicorandil were observed. Results:Smoking was the most frequently associated risk factor. Type I CAE, according to Markis’ classification, was the most prevalent at 60.0%. The values of the baseline FFR in the left anterior descending artery and right coronary artery, following the intracoronary injection of adenosine were both normal, and there were no significant changes in the FFR following the intracoronary injections of nitrate and Nicoronadil. Conclusion:The value of the FFR with CAE was normal, and an intracoronary injection of vasodilators did not change the FFR in patients with CAE. Therefore, vasodilator therapy might be beneficial for patients with symptomatic CAE. (Korean Circulation J 2003;33(1):37-43)

Relationship Between Carotids Sinus Massage, Test With Adenosine and Head-Up Tilt Test in Patients With Syncope

The aim of study was comparison of results of carotids sinus massage (CSM) and adenosine test (AT) in patients with syncope diagnosed by head-up tilt test (HUTT). We observed 169 pts (81 men, 88 women) aged 18-58 yrs (x38,2 yrs) with syncope referred to HUTT. All pts underwent standard HUTT (HUTT-s) acc. To Westminster protocol. Additional tilt with isoproterenol infusion (HUTT-I) was preformed in pts with negative HUTT-s. HUTT was assessed as positive if reproduced symptoms referred by patients. Carotid sinus massage and rapid IV injection of 12 mg of adenosine were done in all pts. RR pauses > 6s induced by adenosine injection or RR pause > 3 s and/or blood pressure fall induced by CSM were assumed as positive tests results. 16 pts (9,5%) had positive AT and 18 pts (10,6%) had positive CSM. Positive AT was observed in 10% pts with negative HUTT-s; in no pts with positive HUTT-s, in 23,1 % of pts with negative HUTT-I and in 8% of positive HUTT-I Positive CSM was observed in 20% pts with negative HUTT-s; in 13,3% pts with positive HUTT-s, in no pts with negative HUTT-I and in 8% of positive HUTT-I Carotid sinus hypersensitivity was no more frequently observed in patients with positive HUTT-I than in positive HUTT-s. Positive AT results were more frequent in pts with negative results of HUTT (both HUTT-s and HUTT-I) Carotid sinus hypersensitivity as a kind of neurocardiogenic syncope seems to have different mechanism than vaso-vagal syncope. HUTT-I rather do not induce syncope by carotid hypersensitivity mechanism. Adenosine may by useful in the diagnosis of syncope in patients with negative results of head-up tilt test.

Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome

As arrhythmias in the long QT syndrome (LQTS) are triggered by heart rate deceleration or acceleration, we speculated that the sudden bradycardia and subsequent tachycardia that follow adenosine injection would unravel QT changes of diagnostic value in patients with LQTS. Patients (18 LQTS and 20 controls) received intravenous adenosine during sinus rhythm. Adenosine was injected at incremental doses until atrioventricular block or sinus pauses lasting 3 s occurred. The QT duration and morphology were studied at baseline and at the time of maximal bradycardia and subsequent tachycardia. Despite similar degree of adenosine-induced bradycardia (longest R-R 1.7+/-0.7 vs. 2.2+/-1.3 s for LQTS and controls, P=NS), the QT interval of LQT patients increased by 15.8+/-13.1%, whereas the QT of controls increased by only 1.5+/-6.7% (P<0.001). Similarly, despite similar reflex tachycardia (shortest R-R 0.58+/-0.07 vs. 0.55+/-0.07 s for LQT patients and controls, P=NS), LQTS patients developed greater QT prolongation (QTc=569+/-53 vs. 458+/-58 ms for LQT patients and controls, P<0.001). The best discriminator was the QTc during maximal bradycardia. Notched T-waves were observed in 72% of LQT patients but in only 5% of controls during adenosine-induced bradycardia (P<0.001). By provoking transient bradycardia followed by sinus tachycardia, this adenosine challenge test triggers QT changes that appear to be useful in distinguishing patients with LQTS from healthy controls.

Fractional flow reserve: can it predict adverse events accurately after coronary stenting?

BACKGROUND FRACTIONAL FLOW RESERVE (FFR) measurements have the ability to predict clinical events in patients after balloon angioplasty and coronary stent implantation. FFR assessment could help identify patients who have a good prognosis and would not benefit from further intervention. OBJECTIVE To determine whether FFR predicts the occurrence of clinical events accurately when adjusted for all available risk factors in patients with single-vessel stenosis treated by stent implantation. DESIGN In this retrospective analysis, men and women were studied who had ischernia when assessed by a stress test or symptoms of disrupted coronary blood flow. For inclusion, patients had to have undergone coronary stent implantation and successful FFR assessment after the procedure. If patients had chronic complete occlusion or acute coronary syndrome they were excluded. INTERVENTION All patients received 100 mg aspirin daily and a bolus dose of 7,000 IU heparin just before stent implantation. A 0.014 inch pressure guidewire and a size 6 or 8 French guiding catheter was used to measure FFR at maximum hyperemia, along with aortic and distal coronary pressure at rest, before stenting. Maximum hyperemia was achieved through intracoronary bolus injection of 30-150pg adenosine. Bare metal stents were used in all patients. For 4 weeks after implantation, patients were given 75mg clopidogrel daily. After the procedure, when hemodynamic conditions had stabilized after the final balloon angioplasty inflation, FFR was re-assessed. Patients' outcomes were recorded by hospital visits and telephone interviews. OUTCOME MEASURES This study measured the occurrence of major adverse cardiac events (MACE): revascularization of the target vessel within 6 months after implantation, myocardial infarction and death. RESULTS The 119 eligible patients (of whom 88 [75%] had been included in the earlier FFR registry) were followed up for 6 months. All patients underwent successful stent implantation and FFR measurements were recorded before and after the procedure for every patient. Average FFR improved significantly from 0.65 before, to 0.94 after stenting (P <0.0001). Of the 18 patients who had a MACE, average FFR after stent implantation was significantly lower than in the 101 patients who remained event-free (0.88 vs 0.95, P=0.001). Multivariate analysis showed that an FFR under 0.95 after stenting was an independent predictor of MACEs (odds ratio 6.22, 95% Cl 1.79-21.62, P = 0.004), along with left-ventricular function (odds ratio 0.95, 95% Cl 0.92-0.99, P=0.021). The risk of a MACE was increased 6 times in patients who had a post-stent FFR under 0.95, compared with patients with a FFR of at least 0.95. CONCLUSION When measured after coronary stenting, FFR can predict the occurrence of death, myocardial infarction and target vessel revascularization effectively. Whether patients with low post-procedural FFR would benefit from further intervention remains to be seen

Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade

The purpose of this study is to evaluate the feasibility of percutaneous antegrade myocardial gene transfer (PAMGT). A consistent and safe technique for in vivo gene transfer is required for clinical application of myocardial gene therapy. PAMGT with concomitant coronary venous blockade was performed in 12 swine. The myocardium was preconditioned with 1 min of occlusion of the left anterior descending and left circumflex arteries. The anterior interventricular vein was occluded during left anterior descending artery delivery, and the great cardiac vein at the entrance of the middle cardiac vein was occluded during left circumflex artery delivery. With arterial and venous balloons inflated (3 min) and after adenosine (25 mug) injection, PAMGT was performed by antegrade injection of an adenoviral solution (1 ml of 10(11) plaque-forming units in each coronary artery) carrying beta-galactosidase or saline through the center lumen of the angioplasty balloon. In one set of animals, PAMGT was performed with selective coronary vein blockade (n = 9); in another set of animals, PAMGT was performed without coronary vein blockade (n = 5). At 1 wk after gene delivery, the animals were killed. Quantitative beta-galactosidase analysis was performed in the left and right ventricular walls. PAMGT was successfully performed in all animals with and without concomitant occlusion of the coronary veins. Quantitative beta-galactosidase analysis showed that PAMGT with coronary blockade was superior to PAMGT without coronary blockade. beta-Galactosidase activity increased significantly in the beta-galactosidase group compared with the saline group: 1.34 +/- 0.18 vs. 0.81 +/- 0.1 ng (P </= 0.01) in the left ventricular wall and 0.91 +/- 0.1 vs. 0.66 +/- 0.07 ng (P </= 0.05) in the right ventricular wall. PAMGT with selective coronary venous blockade is feasible, reproducible, and safely achieved in a large-animal model.

The quantification of absolute myocardial perfusion in humans by contrast echocardiography: Algorithm and validation

We sought to test whether myocardial blood flow (MBF) can be quantified by myocardial contrast echocardiography (MCE) using a volumetric model of ultrasound contrast agent (UCA) kinetics for the description of refill curves after ultrasound-induced microsphere destruction. Absolute myocardial perfusion or MBF (ml.min(-1).g(-1)) is the gold standard to assess myocardial blood supply, and so far it could not be obtained by ultrasound. The volumetric model yielded MBF = rBV.beta/rho(T), where rho(T) equals tissue density. The relative myocardial blood volume rBV and its exchange frequency beta were derived from UCA refill sequences. Healthy volunteers underwent MCE and positron emission tomography (PET) at rest (group I: n = 15; group II: n = 5) and during adenosine-induced hyperemia (group II). Fifteen patients with coronary artery disease underwent simultaneous MCE and intracoronary Doppler measurements before and during intracoronary adenosine injection. In vitro experiments confirmed the volumetric model and the reliable determination of rBV and beta for physiologic flow velocities. In group I, 187 of 240 segments were analyzable by MCE, and a linear relation was found between MCE and PET perfusion data (y = 0.899x + 0.079; r(2) = 0.88). In group II, resting and hyperemic perfusion data showed good agreement between MCE and PET (y = 1.011x + 0.124; r(2) = 0.92). In patients, coronary stenosis varied between 0% to 89%, and myocardial perfusion reserve was in good agreement with coronary flow velocity reserve (y = 0.92x + 0.14; r(2) = 0.73). The volumetric model of UCA kinetics allows the quantification of MBF in humans using MCE and provides the basis for the noninvasive and quantitative assessment of coronary artery disease.

Intracoronary Continuous Adenosine Infusion A Novel and Effective Way of Inducing Maximal Hyperemia for Fractional Flow Reserve Measurement

Various methods are used to induce maximal hyperemia for physiologic studies, but the feasibility and efficacy of continuous intracoronary (IC) infusion of adenosine for measurement of fractional flow reserve (FFR) has not been well-defined. Patients with intermediate coronary artery stenosis were consecutively enrolled. In the phase I study, FFR was measured after 3 dosages of IC adenosine infusion (180, 240 and 300 microg/min) in 30 patients. The phase II study was performed to compare the hyperemic efficacy of IC infusion (240 microg/min) with IC bolus injection (40, 80 microg) and intravenous (IV) infusion (140 microg x kg (-1) x min(-1)) of adenosine in 20 patients. In the phase I study, no significant differences in FFR were observed with the 3 different doses of IC infusion (p = 0.06). In the phase II study, FFR after an IC bolus injection (0.83+/-0.06) was significantly higher than with IV (0.79+/-0.07) or IC (0.78+/-0.09) infusion (p < 0.01). However, no difference in FFR was observed for IC and IV infusions. IC infusion of adenosine seems to be a safe and effective method of inducing maximal hyperemia for FFR measurement.

Paroxysmal Supraventricular Tachycardia in a Patient with Wolff-Parkinson-White Syndrome Induced by Central Venous Cannulation and Surgical Stimuli during Operation: A case report

Wolff-Parkinson-White (WPW) syndrome is a cardiac conduction disorder that presents potentially life-threatening consequences, and it is important that anesthesiologists recognize this syndrome because the sudden development of tachyarrhythmias may result in deleterious hemodynamic changes. We report an episode of severe hemodynamic changes induced by the insertion of a guide wire during central venous cannulation and operation in a 62-yr-old female patient with WPW syndrome. Initially, unstable paroxysmal supraventricular tachycardia was developed during central venous cannulation, which was disappeared immediately upon removing the guide wire. Subsequently, paroxysmal supraventricular tachycardia with severe hemodynamic changes developed 2 hours after operation, and this was successfully treated with an intravenous injection of adenosine, deep anesthesia with sevoflurane and fentanyl, and dopamine infusion. The patient recovered uneventfully after the operation.

Revascularização cirúrgica do miocárdio com enxerto composto de artérias torácica interna esquerda e radial: comparação do fluxo sangüíneo para artéria coronária esquerda com a técnica convencional

INTRODUCAO: Os enxertos compostos tem sido frequentemente utilizados na cirurgia de revascularizacao do miocardio (RM). Entretanto, permanece indefinido se essa tecnica e capaz de oferecer o mesmo fluxo sanguineo (Q) aos ramos da arteria coronaria esquerda (CE) que a tecnica convencional. O objetivo e comparar o Q total aos ramos revascularizados pelas arterias toracica interna esquerda (ATIE) e radial (AR) nas tecnicas compostas e convencional. METODO: Estudamos 42 pacientes distribuidos, aleatoriamente, conforme a tecnica de RM utilizada. Grupo A ou ATIE e AR composta em Y(n=14). Grupo B ou ATIE e AR composta modificada [enxerto intercoronariano com AR e anastomose da ATIE sobreposta a AR ao nivel da arteria interventricular anterior (DA), n=14]. Grupo C ou ATIE pediculada para DA e AR em posicao aorto-coronariana (n=14). Trinta e um pacientes foram submetidos a fluxometria (Fx) com cateter-guia doppler de 12-MHz (0,014 polegada, Flowire, Jometrics Inc.), no pos-operatorio imediato. A reserva de fluxo coronariano (RFC) foi calculada pela determinacao da media da velocidade de pico (APV) em hiperemia apos administracao de adenosina. RESULTADOS: A APV em repouso no inicio da ATIE foi, no grupo A, 28,4±4,8 cm/s; no grupo B, 34,4±7,9 cm/s (p=0,0384 x C) e, no grupo C, 25,8± 8,6 cm/s. A RFC foi de 2,1 ± 0,4, 2 ± 0,3 e 2±0,4 nos grupos A, B e C, (p=0,7208). O Q total distribuido aos ramos da CE revascularizados foi, no grupo A, 110±30 ml/min, no grupo B, 145±59 ml/min e, no grupo C, 133±58 ml/min (p=0,3232 A, B x C). CONCLUSOES: Nao houve diferenca significativa do Q total oferecido ao territorio da CE revascularizado pelas tecnicas de EC e convencional. A RFC da ATIE nos grupos compostos foi satisfatoria.

Adenosinergic and cholinergic control mechanisms during hypoxia in the epaulette shark (Hemiscyllium ocellatum), with emphasis on branchial circulation

Coral reef platforms may become hypoxic at night during low tide. One animal in that habitat, the epaulette shark (Hemiscyllium ocellatum), survives hours of severe hypoxia and at least one hour of anoxia. Here, we examine the branchial effects of severe hypoxia (<0.3 mg oxygen l(-1) for 20 min in anaesthetized epaulette shark), by measuring ventral and dorsal aortic blood pressure (P(VA) and P(DA)), heart rate (fh), and observing gill microcirculation using epi-illumination microscopy. Hypoxia induced a flow of blood in two parallel blood vessels, termed longitudinal vessels, in the outer borders of the free tip of the gill filament. Hypoxia also induced significant falls in fh, P(VA) and P(DA), and a biphasic change in ventilation frequency (increase followed by decrease). Adenosine injection (1 micromol kg(-1)) also initiated blood flow in the longitudinal vessels, in addition to significant drops in P(VA), P(DA) and fh, and a biphasic response in ventilation frequency (decrease followed by increase) indicating that adenosine influences ventilation. Aminophylline (10 mg kg(-1)), an A(1) and A(2) adenosine receptor antagonist, blocked the effects of adenosine injection, and also significantly reduced blood flow in the longitudinal vessels during hypoxia. In the second part of the study, we examined the cholinergic influence on the cardiovascular circulation during severe hypoxia (<0.3 mg l(-1)) using antagonists against muscarinic (atropine 2 mg kg(-1)) and nicotinic (tubocurarine 5 mg kg(-1)) receptors. Injection of acetylcholine (ACh; 1 micromol kg(-1)) into the ventral aorta caused a marked fall in fh, a large increase in P(VA), but small changes in P(DA) (suggesting increased R(gill)). Atropine was able to inhibit the branchial vascular responses to ACh but not the hypoxic bradycardia, suggesting the presence of muscarinic receptors on the heart and gill vasculature, and that the hypoxia induced bradycardia is of non-cholinergic origin. The results suggest that adenosine mediates increases in the arterio-venous circulation in the gill during hypoxia. This may serve to increase blood supply to heart and gill tissue.

Myocardial bridging is associated with alteration in coronary vasoreactivity

Shear stress alteration has been recognized as a predisposing factor for the impairment of endothelial function. Myocardial bridging is a congenital condition associated with alteration in shear stress, however, its impact upon vasoreactivity remains undetermined. This was a case-control designed study with 29 patients with myocardial bridging and 58 patients without myocardial bridging. Endothelium-dependent and endothelium-independent changes in coronary artery diameters, blood flow and wall shear stress were determined after intracoronary infusion of acetylcholine (ACH, 10(-6)-10(-4) mol/L) and nitroglycerine (NTG, 200 microg). Coronary flow velocity reserve (CFVR) was determined after intracoronary injection of adenosine (18-36 microg). In response to ACH, there was more epicardial vasoconstriction at the myocardial bridging site compared with the proximal and distal segments (-29.6+/-21.7 vs. -9.6+/-22.5 and -17.4+/-21.5%, p<0.05) and compared with the control group (-29.6+/-21.7 vs. -5.9+/-36.5%, p<0.001). The response to NTG and CFVR was the same in the case and the control group. Wall shear rate (WSR) was higher in the MB site at baseline and in response to ACH. MB is characterised by enhanced WSR and impairment in endothelium-dependent vasorelaxation. These functional alterations may add to the severity of structural lumen compression and thus to the clinical presentation of this congenital abnormality.

Inoculation of bacille calmette guerin combined with intraperitoneal adenosine injection enhances antibacterial effect of macrophage against Mycobacterium tuberculosis in mice

The protection rate of inoculation with BCG vaccine is only 50 percent, and most of patients with tuberculosis had a history of BCG vaccine inoculation. Adenosine (ADO) has an immunomodulating effect; it promotes immune reaction by increasing number of macrophage and enhancing phagocytosis. The present study was designed to investigate if combined use of adenosine with BCG enhances the anti-Mycobacterium tuberculosis effect of macrophage in mice. Fifty BALB/C mice were divided randomly into 3 groups: BCG group (n = 21), BCG plus ADO group (n = 21) and control group (n = 8). The mice in BCG and BCG plus ADO groups were inoculated with 0.1 ml BCG intradermally and the mice in BCG plus ADO group were injected intraperitoneally with ADO 30 mg/(kg.d) for 5 days. The mice in BCG group and control group were injected with NS 0.1 ml/d for 5 days. Six weeks after the last injection, all mice were challenged with intravenous 1 x 10(6) CFU human Mycobacterium tuberculosis virulent strain. After challenging, lung and spleen specimens were taken at the 10th, 20th and 30th days from the mice of BCG and BCG plus ADO groups and at the 30th day from mice in control group. The pathological examinations of lung and spleen sections were performed after HE staining and acid-fast staining, and detection of cell apoptosis was also performed. Consolidation with neutrophil infiltration was found in most of the lung tissue taken at the day 30; there were a lot of tuberculous granulomas and Mycobacterium tuberculosis in the lungs of control group. The alveolar septum in BCG gradually became wide and in interstitium lymphocyte infiltration dominated, and there were less tuberculous granulomas but there were large number of Mycobacterium tuberculosis in the lungs from 10th to 30th days after challenging. The widening of alveolar septum and consolidation of lung tissue in BCG plus ADO group became milder with monocytes infiltration, and there were few tuberculosis granulomas and Mycobacterium tuberculosis in the lungs from 10th to 30th days after challenging. ADO could increase the number of monocyte-macrophages and promoted anti-bacterial effects of these cells.

Focally injected adenosine prevents seizures in the rat

Prophylactic drug injection directly onto a seizure focus has the potential to improve seizure control with fewer side effects than is produced by systemic therapy. Using a dose-response model, we evaluated the effectiveness of adenosine application for focal seizure prophylaxis in 12 rats. Total spikes and electroencephalographic ictal events were reduced significantly by treatment with adenosine compared to control (P < 0.0001). This study demonstrates effectiveness and feasibility in a model system using intracranial injection of adenosine to prevent epileptiform events.

Role of mitochondrial aldehyde dehydrogenase in nitroglycerin-induced vasodilation of coronary and systemic vessels: an intact canine model.

It has recently been shown that mitochondrial aldehyde dehydrogenase 2 (mtALDH) catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from nitroglycerin (glyceryl trinitrate [GTN]) within mitochondria, leading to production of cGMP and vasorelaxation. However, whether this mechanism operates in the systemic and coronary beds that subserve the antianginal action of GTN is not known. In this study, we address this question in an intact canine model. Fourteen healthy mongrel dogs (weight, 20 to 25 kg) were studied. Coronary blood flow and hemodynamics were continuously monitored by a pulse Doppler flow probe implanted around the left circumflex coronary artery and with catheters in left ventricle and aorta, respectively. Each dog was given a 1-mL bolus injection of GTN, sodium nitroprusside (SNP), or adenosine through a catheter in the left atrium before and 30 minutes after infusion of cyanamide (17 mg/kg), an inhibitor of mtALDH. Cyanamide significantly inhibited both the classic dehydrogenase and GTN reductase activities of mtALDH in situ and attenuated the coronary blood flow increase and declines in blood pressure and left ventricular end-diastolic pressure produced by GTN in vivo. In contrast, mtALDH inhibition had no effect on the coronary and systemic effects of SNP and adenosine. Our data suggest that mtALDH contributes to GTN biotransformation in vivo and thus at least partly underlies the antianginal mechanism of drug action. Our findings also highlight the differences in biometabolism of clinically relevant nitrosovasodilators.

Stimulation of vagus nerve modifies negative chronotropic and hypotensive effects of adenosine.

The effects of electrical stimulation of the vagus nerve on the negative chronotropic and hypotensive effects of adenosine were studied on adult rats. Intravenous injection of adenosine to control rats significantly reduced the heart rate and induced a transient blood pressure drop followed its increase. Preliminary electrical stimulation of the right vagus nerve reduced the magnitude and duration of adenosine-induced bradycardia and changed the dynamics of adenosine-induced arterial pressure perturbations.

Diastolic coronary vascular reserve: a new index to detect changes in the coronary microcirculation in hypertrophic cardiomyopathy

ObjectivesThe present study introduces a modification of the diastolic coronary conductance concept that maintains its sensitive properties to detect changes in the coronary microcirculation in human hypertrophy. BackgroundDecrements of coronary flow in hypertrophy have been explained by changes in the coronary microcirculation. No measure is available to detect these changes. MethodsDoppler velocity catheters were introduced into the left anterior descending artery (LAD) and left circumflex coronary artery (LCx) of patients with obstructive hypertrophic cardiomyopathy (HCM) (n = 11) and into the LAD of cardiac transplant recipients (n = 9). The diastolic coronary conductance was measured at rest and after maximal hyperemia induced by a bolus injection of adenosine. Diastolic coronary vasodilator reserve (DCVR) was calculated as the hyperemic diastolic coronary conductance, divided by the coronary conductance during resting conditions. ResultsLeft ventricular outflow tract gradient in the HCM group (83 ± 31 mm Hg) was significantly higher (p < 0.05). Septal wall thickness was significantly increased (p < 0.05), while wall thickness was unchanged in the posterior wall of the HCM group. The coronary flow reserve was significantly decreased in the HCM-LCx region (to 64 ± 7% of control) and in the HCM-LAD regions (to 57 ± 7% of control). The DCVR was only decreased in the HCM-LAD (to 46 ± 3% of control) and not in the HCM-LCx group (86 ± 6%, p > 0.05). Esmolol did affect the pressure gradient and systolic shortening, but did not affect the maximal diastolic conductance. ConclusionsThe DCVR, in contrast with the coronary flow reserve, is decreased in those regions that display a disturbance in the microcirculation and may, therefore, offer a new way to study coronary adaptations in patients with hypertrophy.

178 Quantitative evaluation of regional myocardial perfusion during dipyridamole stress by real-time myocardial contrast echocardiography in patients with and without coronary artery disease

178 Quantitative evaluation of regional myocardial perfusion during dipyridamole stress by real-time myocardial contrast echocardiography in patients with and without coronary artery disease

Coronary flow reserve in the newborn lamb: an intracoronary Doppler guide wire study.

Recent studies indicate a severely reduced coronary flow reserve (CFR) in neonates with congenital heart disease. The significance of these studies remains debatable, as the ability of the anatomically normal neonatal heart to increase coronary flow is currently unknown. This study was designed to establish normal values for CFR in newborns after administration of adenosine [pharmacologic CFR (pCFR)] and as induced by acute hypoxemia (reactive CFR). Thirteen mechanically ventilated newborn lambs were studied. Coronary flow velocities were measured in the proximal left anterior descending coronary artery before and after adenosine injection (140 and 280 microg/kg i.v.) using an intracoronary 0.014-in Doppler flow-wire. Measurements were made at normal oxygen saturation (SaO(2)) and during progressive hypoxemia induced by lowering the fraction of inspired oxygen. CFR was defined as the ratio of hyperemic to basal average peak flow velocity. In a hemodynamically stable situation with normal SaO(2), pCFR was 3.0 +/- 0.5. pCFR decreased with increasing hypoxemia. Regression analysis showed a linear relation between SaO(2) and pCFR (R = 0.86, p < 0.0001). Reactive CFR obtained at severe hypoxemia (Sao(2) <30%) was 4.2 +/- 0.8, and no significant further increase in coronary flow velocity occurred by administration of adenosine. Newborn lambs have a similar capacity to increase coronary flow in response to both pharmacologic and reactive stimuli as older subjects. Administration of adenosine does not reveal the full capacity of the newborn coronary circulation to increase flow, however, as the flow increase caused by severe hypoxemia is significantly more pronounced.

Interaction of carbon monoxide and adenosine in the nucleus tractus solitarii of rats.

Carbon monoxide has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to carbon monoxide and biliverdin. Previously, we have shown the involvement of carbon monoxide in central cardiovascular regulation, baroreflex modulation, and glutamatergic neurotransmission in the nucleus tractus solitarii of rats. We also showed that adenosine increased the release of glutamate in the nucleus tractus solitarii. In this study, we investigated the possible interactions of carbon monoxide and adenosine in the nucleus tractus solitarii. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of increasing doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by heme oxygenase to yield carbon monoxide, produced a significant decrease in blood pressure and heart rate in a dose-dependent manner. In addition, similar cardiovascular effects were observed after injection of adenosine (2.3 nmol). These cardiovascular effects of hemin were attenuated by prior administration of the adenosine receptor antagonist 1,3-dipropyl-8-sulfophenylxanthine. Similarly, pretreatment of the heme oxygenase inhibitor zinc protoporphyrin IX or zinc deuteroporphyrin 2,4-bis glycol also attenuated the depressor and bradycardic effects of adenosine. These results indicate that the interaction between carbon monoxide and adenosine may contribute to the activation of heme oxygenase in central cardiovascular regulation.