Injection Of Adenosine Research Articles

Adenosine-enhanced ischemic preconditioning provides enhanced postischemic recovery and limitation of infarct size in the rabbit heart

Objective: The purpose of this study was to determine the effect of an intracoronary bolus injection of adenosine used in concert with ischemic preconditioning on postischemic functional recovery and infarct size reduction in the rabbit heart and to compare adenosine-enhanced ischemic preconditioning with ischemic preconditioning and magnesium-supplemented potassium cardioplegia. Methods: New Zealand White rabbits ( n = 36) were used for Langendorff perfusion. Control hearts were perfused at 37° C for 180 minutes; global ischemic hearts received 30 minutes of global ischemia and 120 minutes of reperfusion; magnesium-supplemented potassium cardioplegic hearts received cardioplegia 5 minutes before global ischemia; ischemic preconditioned hearts received 5 minutes of zero-flow global ischemia and 5 minutes of reperfusion before global ischemia; adenosine-enhanced ischemic preconditioned hearts received a bolus injection of adenosine just before the preconditioning. To separate the effects of adenosine from adenosine-enhanced ischemic preconditioning, a control group received a bolus injection of adenosine 10 minutes before global ischemia. Results: Infarct volume in global ischemic hearts was 32.9% ± 5.1% and 1.03% ± 0.3% in control hearts. The infarct volume decreased (10.23% ± 2.6% and 7.0% ± 1.6%, respectively; p < 0.001 versus global ischemia) in the ischemic preconditioned group and control group, but this did not enhance postischemic functional recovery. Magnesium-supplemented potassium cardioplegia and adenosine-enhanced ischemic preconditioning significantly decreased infarct volume (2.9% ± 0.8% and 2.8% ± 0.55%, respectively; p < 0.001 versus global ischemia, p = 0.02 versus ischemic preconditioning and p = 0.05 versus control group) and significantly enhanced postischemic functional recovery. Conclusions: Adenosine-enhanced ischemic preconditioning is superior to ischemic preconditioning and provides equal protection to that afforded by magnesium-supplemented potassium cardioplegia. (J Thorac Cardiovasc Surg 1998;116:154-62)

Renal haemodynamic responses to exogenous and endogenous adenosine in conscious dogs.

1. Adenosine has been suggested to be the mediator of a metabolic feedback mechanism which transfers acute changes in the tubular load into opposite changes in renal blood flow (RBF). The goal of the present experiments was to assess the importance of endogenously formed adenosine as a 'homeostatic metabolite' during short-term changes in metabolic demand. 2. In nine chronically instrumented conscious foxhounds, both the direct effects of adenosine injections (10, 30 and 100 nmol) into the renal artery and the temporal changes of RBF after short renal artery occlusions (15, 30 and 60 s duration), the most widely used experimental model to study the metabolic feedback mechanism in vivo, were studied. 3. Intrarenal bolus injections of adenosine (10, 30 and 100 nmol) induced dose-dependent decreases of RBF (RBF: -34 +/- 5, -59 +/- 4 and -74 +/- 4 %, respectively). This vasoconstrictor effect of adenosine was significantly larger (RBF: -51 +/- 4, -68 +/- 4 and -83 +/- 3 %, respectively) when the dogs received a low salt diet. 4. The post-occlusive responses were characterized by a transient hyperaemia with no detectable drop of RBF below the preocclusion level. The post-occlusive responses were affected neither by changes in local angiotensin II levels, nor by intrarenal infusions of hypertonic NaCl or blockade of A1 adenosine receptors. 5. When intrarenal adenosine levels were elevated by infusion of the adenosine uptake inhibitor dipyridamole, a transient, although weak, post-occlusive vasoconstriction was detected. 6. In summary, the present data demonstrate that adenosine acts as a potent renal vasoconstrictor in the conscious dog. The endogenous production of adenosine during short-lasting occlusions of the renal artery, however, appears to be too small to induce a post-occlusive vasoconstrictor response of RBF. These results suggest that a metabolic feedback with adenosine as 'homeostatic metabolite' is of minor importance in the short-term regulation of RBF in the conscious, unstressed animal.

Stimulation of Duodenal Bicarbonate Secretion by Carbenoxolone in Rats: A Comparative Study with Prostaglandin E 2

1. The effects of carbenoxolone on duodenal HCO − 3 secretion were examined in anesthetized rats and compared with those of prostaglandin E 2 (PGE 2). 2. After 18-hr fasting, the duodenal loop (1.7 cm) that was made between the pyloric ring and the area just proximal to the outlet of the common bile duct was perfused with saline (pH 4.5), the pH of perfusate and the transmucosal potential difference (PD) were continuously monitored and HCO − 3 output was determined by titration with 10 mM HCl. 3. Under these conditions, duodenal pH, PD, and HCO − 3 secretion were increased in response to PGE 2 (0.3 and 1.0 mg/kg) given intravenously as a single injection. Carbenoxolone (0.1–1.0 mg/kg, intravenously) also caused an increase in duodenal pH and HCO − 3 output in a dose-dependent manner, with a concomitant rise in PD; at 1 mg/kg, the magnitude of HCO − 3 output was almost equivalent to that induced by PGE 2 at 0.3 mg/kg. 4. Prior administration of indomethacin, a cyclooxygenase inhibitor (5 mg/kg, subcutaneously), did not affect the HCO − 3 stimulatory action of carbenoxolone or PGE 2. 5. Duodenal HCO − 3 secretion was also increased by intravenous injection of dibutylyl adenosine 3′,5′-cyclic monophosphate (dbcAMP) but not by isobutylmethyl xanthine (IBMX; 10 mg/kg), an inhibitor of phosphodiesterase, but the former action was significantly potentiated in the presence of IBMX. Likewise, the pretreatment of IBMX significantly enhanced the HCO − 3 stimulatory action of PGE 2 but had no effect on the HCO − 3 response induced by carbenoxolone. 6. These results suggest that carbenoxolone stimulates duodenal HCO − 3 secretion in rats, similar to PGE 2 and this mechanism does not involve endogenous prostaglandins and is not associated with the intracellular accumulation of cAMP.

Role of pulmonary C fibers in adenosine-induced respiratory inhibition in anesthetized rats.

The clinical use of adenosine is commonly associated with pulmonary side effects, namely dyspnea, that suggest the possible involvement of bronchopulmonary sensory afferents. Our objective in this study was to characterize the effects of adenosine on breathing and to determine whether the vagal pulmonary afferents play a role in mediating these effects. We measured respiratory and cardiovascular changes in anesthetized, spontaneously breathing rats after bolus injections of adenosine at therapeutic doses. Right atrial injection of adenosine (0.04-0.6 mg/kg) elicits, in a dose-dependent manner, a pulmonary chemoreflex-like response consisting of a delayed apnea, bradycardia, and hypotension. In contrast, the classic capsaicin-elicited pulmonary chemoreflex occurs immediately after injection. Perineural capsaicin treatment of the cervical vagi blocked the adenosine-induced respiratory inhibition. Left ventricular administration of adenosine failed to elicit an apneic response. Pretreatment with the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine attenuated the adenosine-induced apnea. These results indicate that adenosine elicits a respiratory inhibition via stimulation of pulmonary C fibers and that activation of the A1-receptor is probably involved. It is unclear, however, what accounts for the exceedingly long latency in this response.

Impaired flow-mediated vasodilation of epicardial coronary artery in vasospastic angina.

To evaluate whether the flow-mediated vasodilation and coronary flow reserve are impaired or not in patients with vasospastic angina (VA), we measured the changes of epicardial coronary artery diameter and flow reserve in spasm related-left anterior descending coronary artery (LAD). The flow mediated-response of epicardial coronary arteries in 15 VA were compared with 15 controls. Using quantitative coronary angiography, we measured the diameter of proximal (pLAD) and middle segment (mid-LAD) of LAD under baseline conditions, during increased blood flow after distal adenosine injection and after proximal administration of nitroglycerin. An increased fraction of average peak velocity after injection of adenosine was similar in both groups [control 340 (mean)+/-24 (SEM)%; VA 330+/-19%]. Flow-mediated vasodilation was preserved in all controls (pLAD 13.1+/-1.4%; mid-LAD 15.8+/-2.5%) but it was significantly impaired in patients with VA (pLAD -1.0+/-1.8%; mid-LAD 0.1+/-3.5%). The vasodilator response to nitroglycerin was comparable in controls (pLAD 25.8+/-2.8%; mid-LAD 27.2+/-2.8%) and VA (pLAD 26.2+/-5.2%; mid-LAD 26.7+/-3.5%). Coronary flow reserve is preserved in patients with VA. However, the flow-mediated response of spasm related-epicardial coronary artery is impaired. This may play an important role in the pathogenesis of coronary artery spasm.

Phasic Coronary Artery Flow Profiles in Patients with Aortic Valve Disease

Background:The previous reports have demonstrated that coronary artery flow profiles might change in patie- nts with aortic valve disease. Our objective was to assess phasic coronary artery flow and velocity characteristics and coronary flow reserve in patients with severe aortic vale disease. Method:We studied six patients (4 men and 2 women, mean age 61.3±6.3 years with aortic regurgitation and seven patients (3 men and 4 women, mean age 66.3±10.3 years with aortic stenosis. Coronary flow velocity was measured at the proximal portion of left anterior descending artery with 0.014-inch Doppler tipped guide wire and intracoronary injection of adenosine. Nineteen patients (11 men and 8 women, mean age 52±9.8 years with normal coronary artery were served as normal control. Result:The velocity-time integral of systolic coronary flow (SPVi was significantly higher in patient with severe aortic regurgitation than control (21.1±5 vs 9.4±3.1, p 0.05, respe- ctively. Coronary flow reserve was significantly decreased in patient with aortic valve disease compared with control subject (2.1±0.8 vs 3.2±0.4 p<0.05, respectively. Conclusion:Coronary flow reserve decreased signi- ficantly in patients with AR and with AS compared with normal control. Coronary blood flow profiles in patients with AR was characterized by systolic flow predominance and reduced diastolic flow whereas patients with AS was a tendency toward decreased systolic flow and increased diastolic flow. ( ( ( (Korean Circulation J 1998;28

Safety issues in the treatment of paediatric supraventricular tachycardias.

Paroxysmal supraventricular tachycardia caused by atrioventricular re-entry is the most frequent arrhythmia in children of all age groups. It represents the most frequent clinical situation where antiarrhythmic drug therapy has to be considered in a child. Acute termination of an episode of tachycardia in all paediatric age groups is nowadays best achieved with an intravenous bolus injection of adenosine. Since the introduction of adenosine into clinical practice, the need to proceed to electrocardioversion has been limited to the infant (or in rare cases an older child) with severe cardiovascular collapse. In the haemodynamically stable infant or child, several other antiarrhythmic agents such as flecainide or propafenone can be used with relative safety and with a high probability of immediate success. The same is true for verapamil, although intravenous administration should be avoided in the first year of life. In newborns and in infants with first presentation of an episode of tachycardia, drug prophylaxis of recurrences is usually recommended for the whole of the first year of life. Prophylactic treatment may consist of oral digoxin as first choice, with a beta-blocker as an alternative. In an infant with Wolff-Parkinson-White syndrome it may be wise to avoid digoxin and to start treatment with a beta-blocker. Antiarrhythmic class Ic drugs such as propafenone or flecainide, and the class III agent sotalol, are widely used as the next steps of therapy when digoxin and beta-blockers fail to prevent recurrences. These agents are about equivalent with regard to their efficacy and risk profile. Amiodarone is considered to be an agent that should be reserved for use in situations when the tachycardia is refractory to the previously named agents. Older children may commence treatment with a beta-blocker and the subsequent steps of treatment are the same as those for infants. Curative catheter ablation of accessory pathways has been shown to be as efficient and well tolerated in the paediatric age group as it is in adults. This treatment option is nowadays quite often offered to older children. However, in infants and smaller children, ablation is used as a last resort. Rare forms of paediatric supraventricular tachycardia (other than atrioventricular re-entry through the atrioventricular node or accessory pathways) are occasionally difficult to treat and present special problems. For each of these arrhythmias, a specially tailored individual therapeutic approach is needed.

Invited editorial on "Femoral arterial injection of adenosine in humans elevates MSNA via central but not peripheral mechanisms".

the exercise pressor reflex ([8][1]) is widely believed to make an important contribution to the cardiovascular and respiratory responses evoked by exercise. Much is known about this reflex. For example, its afferent limb is composed of group III afferents, the axons of which are thinly myelinated,

A chronic model to simultaneously measure intracranial pressure, cerebral blood flow, and study the pial microvasculature

In an effort to study changes in cerebral blood flow (CBF), intracranial pressure (ICP) and intracranial compliance (ICC) simultaneously, we have developed a chronic model in rats using a pial window crown with two ports. This model can also be used to study vasoreactivity of pial vessels. Female Sprague–Dawley rats weighing between 225–250 g underwent placement of cranial chamber with dual ports under pentobarbital anesthesia. To test the utility of this technique 45 groups of rats were studied. Group 1 consisted of control animals. Group 2 consisted of rats undergoing 15 min of global cerebral ischemia. Rats in group 3 were evaluated for changes in vessel diameter and ICP after adenosine injection. In group 4 leukocyte/endothelial interactions were evaluated. These groups demonstrate the ability of this model to monitor CBF, ICP, ICC and pial vessel architecture in chronic rat experiments.

Cyanide suppression of inwardly rectifying K+ channels in guinea pig chromaffin cells involves dephosphorylation.

Treatment of chromaffin cells with cyanide induced a gradual decrease in an inwardly rectifying K+ current (IIR), and washout of the mitochondrial inhibitor resulted in a rapid recovery of IIR. This diminution of IIR was reversed in a time-dependent manner by infusion of ATP or UTP, but not by that of GTP, ITP, or CTP. The restoration by ATP was not altered by addition to the pipette solution of 50 microM fluorescein 5-isothiocyanate, an inhibitor of various ATPases. A similar recovery of IIR occurred with injection of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), but not of 5'-adenylylimidodiphosphate or alpha,beta-methyleneadenosine 5'-triphosphate. The ATP gamma S effect was biphasic, resulting in first a run-up of the current in ATP-depleted cells followed by a rundown of the current. This rundown was almost abolished by addition of guanosine 5'-O-(2-thiodiphosphate) to the ATP gamma S solution, suggesting the involvement of a G protein. Bath application of the protein kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine at 100 microM, but not N-(2-[methylamino]-ethyl)-5-isoquinolinesulfonamide, induced a reversible inhibition of IIR in the presence of pipette ATP, and the inhibition was diminished by 1 microM calyculin A, a phosphatase inhibitor. Bath application of 1 microM phorbol 12,13-dibutyrate did not affect IIR. It is concluded that cyanide suppresses inward rectifier K+ channel activity via dephosphorylation and that protein kinase C, adenosine 3',5'-cyclic monophosphate-dependent kinase, or guanosine 3',5'-cyclic monophosphate-dependent kinase is not involved in modulation of the channel.

Influence of Beta-Adrenergic and Vagal Activity on the Effect of Exogenous Adenosine on Supraventricular Tachycardia Termination

Adenosine, which binds to cell surface receptors and couples with guanosine triphosphate-binding inhibitory proteins (Gi), is potent in terminating supraventricular tachycardia (SVT). However, whether the differences in autonomic tone will influence this effect remains unknown. This study was designed to investigate the role of β-adrenergic and vagal activity on the action of adenosine. Forty patients with clinically documented SVT (22 with atrioventricular node reentrant tachycardia and 18 with atrioventricular reciprocating tachycardia) were divided into 4 groups with 10 patients in each group. In groups 1 and 2, adenosine was intravenously injected during the baseline state and during infusion of isoproterenol (2 and 4 μg/min, respectively). Group 2 patients received atropine (0.04 mg/kg) injection before isoproterenol infusion. In groups 3 and 4, intravenous injection of adenosine was given during the baseline state and after injection of atropine (0.02 and 0.04 mg/kg, respectively). Group 4 patients received propranolol (0.2 mg/kg) before atropine injection. The minimal dose of adenosine to terminate tachycardia during isoproterenol infusion of 2 μg/min was greater than that during the baseline state in both groups 1 and 2. The minimal dose of adenosine during isoproterenol infusion with 4 μg/min was higher than that with 2 μg/min in group 2, but not in group 1 patients. In both groups 3 and 4, the minimal dose of adenosine required to terminate tachycardia during atropine injection with 0.02 mg/kg was greater than that during the baseline state. The minimal effective dose of adenosine during atropine injection with 0.04 mg/kg was higher than that with 0.02 mg/kg in group 4, but not in group 3 patients. In conclusion, either limb of the autonomic nervous system may modulate the adenosine dosage required for termination of SVT. Patients taking drugs such as β blockers or vagolytic agents may need alterations in the dose of adenosine for therapy.Infusion of isoproterenol or atropine increased the minimal effective dose of intravenous adenosine required for termination of supraventricular tachycardia. This suggested that differences in autonomic tone may influence the effects of adenosine.

Dose and rate-dependent effects of adenosine on atrial action potential duration in humans.

Adenosine provokes atrial fibrillation (AF) in some patients with paroxysmal supraventricular tachycardia (PSVT). Which patients are more susceptible to develop atrial fibrillation after the administration of adenosine to terminate PSVT is unknown. We prospectively measured atrial action potential duration (APD) at incremental doses of 3, 6, and 12 mg of adenosine at paced cycle lengths (CLs) of 600, 500, and 400 ms in 25 patients. Bolus injection of adenosine decreased APD at 90% repolarization in a dose- and rate-dependent manner. During paced CLs of 600, 500, and 400 ms, decreases of 8%, 13%, and 19% (p < 0.05), respectively, were found after bolus administration of 3 mg of adenosine. After 6 mg of adenosine, the APD shortened by 12%, 19%, (p < 0.05), and 27% (p < 0.01), respectively. After 12 mg of adenosine, the APD shortened by 15%, 27% (p < 0.05), and 38% (p < 0.01), respectively. Transient AF occurred in 4 of 25 (16%) patients, all during paced CLs of 400 ms, and after adenosine 6 mg in one patient and 12 mg in three patients. Adenosine shortens atrial action potential duration in a dose- and rate-dependent manner. Whether patients with faster rates during PSVT and those given higher doses of adenosine are more prone to develop atrial fibrillation remains to be determined.

Modification of cardiovascular response of adenosine A 1 receptor agonist by cyclic AMP in the spinal cord of the rats

This study was performed to investigate the influence of the spinal adenosine A 1 receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by cyclic AMP (cAMP) or cyclic GMP (cGMP). Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawyley rats. Injection (i.t.) of adenosine A 1 receptor agonist, N 6-cyclohexyladenosine (CHA; 1, 5 and 10 nmol) produced dose dependent decrease of BP and HR. Pretreatment with a cAMP analogue, 8-bromo-cAMP, attenuated the depressor and bradycardiac effects of CHA (10 nmol), but not with cGMP analogue, 8-bromo-cGMP. These result suggest that adenosine A 1 receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that this depressor and bradycardiac actions are mediated by cAMP.

Effects of verapamil, propranolol, and procainamide on adenosine-induced negative dromotropism in human beings

Adenosine, verapamil, propranolol, and pracainamide are widely used antiarrhythmic drugs. The interactions among them are still not known in human beings. Adenosine-induced negative dromotropic effects were assessed by rapid bolus injection of adenosine during constant high right atrial pacing in each patient. The initial dose of adenosine was 0.5 mg and was followed by a stepwise increment of 0.5 mg until atrioventricular (AV) nodal block occurred. The negative dromotropic actions of adenosine were examined in the control state and in the following three protocols in three groups of patients: (1) In 12 patients (group 1), intravenous verapamil, 0.15 mg/kg, was given; (2) in 12 patients (group 2), intravenous propranolol, 0.1 mg/kg, was given; and (3) in 10 patients (group 3), intravenous procainamide, 15 mg/kg, was given. The dose—response curves of adenosine on AV nodal conduction were almost identical in the control state and after verapamil, propranolol, or procainamide injection. However, verapamil, in contrast to propranolol, significantly reduced the dose of adenosine required to produce AV nodal block, from 4.4 ± 0.7 mg to 2.7 ± 0.3 mg ( p < 0.01). Of note, procalnamide exerted no significant effects on adenosine-induced negative dromotropism on AV nodal conduction or AV nodal block. In conclusion, the negative dromotropic effects of adenosine are preserved and independent even in the presence of verapamil, propranolol, or procainamide. Both verapamil and propranolol can exhibit additive effects with adenosine in prolonging AV nodal conduction time; however, only verapamil can reduce the dose of adenosine required to produce AV nodal block. This finding indicates that the dose of adenosine may be reduced for patients who have already been treated with verapamil.

Branchial and systemic roles of adenosine receptors in rainbow trout: an in vivo microscopy study.

The purinergic branchial vasomotor control in rainbow trout (Oncorhynchus mykiss) was studied using an epi-illumination microscope equipped with a water-immersion objective. Cardiac output (Q), heart rate, and dorsal (PDA) and ventral (PVA) aortic pressures were recorded simultaneously. Prebranchial injection of adenosine or the A1-receptor agonist N6-cyclopentyl-adenosine (CPA) constricted the distal portion of the filament vasculature, which coincided with an increase of PVA. The A2-receptor agonist PD-125944 was without effect. After adenosine and CPA injection, an overflow of blood to the secondary system was repeatedly observed unless blood flow came to a complete stop. The lack of a concomitant reduction of Q suggested a redistribution of blood to the secondary system and to more proximal parts of the filament. The branchial effects of adenosine and CPA were completely blocked by the unspecific adenosine receptor antagonist amino-phylline and the specific A1-receptor antagonist N6-cyclopen-tyltheophylline. The results suggest that A1-receptors alone mediate the branchial vasoconstriction observed. Thus the responses of the branchial vasculature to adenosine include a vasoconstriction of the filament vasculature mediated via specific A1 receptors and a redistribution of blood flow to the secondary system and to proximal parts of the filament. Additional cardiovascular effects of adenosine included decreased systemic vascular resistance and heart rate.

Adenosine: Potential modulator for vasovagal syncope

Objectives. This study examined the hypothesis that adenosine could provoke a vasovagal response in susceptible patients. Mechanisms of the vasovagal response were further explored by studying the adenosine-mediated reactions.Background. Increased sympathetic activity is frequently observed before vasovagal syncope. Recent studies have demonstrated that adenosine, in addition to its direct bradycardiac and vasodilatory effects, can increase sympathetic discharge by activating cardiovascular afferent nerves.Methods. The effects of adenosine and head-up tilt-table testing with or without isoproterenol were prospectively evaluated in 85 patients examined for syncope after negative results of electro-physiologic testing (51 men and 34 women, mean [± SD] age 61 ± 17 years). Adenosine bolus injections of 6 mg and 12 mg were sequentially administered to patients in the upright position. The same protocol was implemented in 14 normal control subjects (7 mean and 7 women, men [± SD] age 38 ± 10 years).Results. Transient hypertension or tachycardia was observed in 57 (67%) and 20 (24%) patients after administration of 6 mg and 12 mg of adenosine, respectively, during the immediate phase (first 15 s), suggesting direct sympathetic activation. Hypotension and reflex tachycardia were observed in all patients during the delayed phase (15 to 60 s after adenosine injection), suggesting baroreceptor unloading. A vasovagal response was induced in 22 (26%) and 29 (34%) patients after adenosine administration and during tilt-table testing. Inducibility of a vasovagal response by these two methods was comparable (p = 0.12). Of the control subjects, one (7%) had a vasovagal response after adenosine administration and one (7%) had a positive response during tilt-table testing.Conclusions. These observations support the idea that adenosine is an endogenous modulator of the cardiac excitatory afferent nerves. Sympathetic activation by adenosine can be direct (i.e., cardiac excitatory afferent nerves) and indirect (i.e., vasodilation and reflex sympathetic activation). Adenosine could be an important modulator in triggering a vasovagal response in susceptible patients during examination for syncope.

Intramyocardial injections and protection against myocardial ischemia. An attempt to examine the cardioprotective actions of adenosine.

Although adenosine has been proposed to be a cardioprotective agent, direct examination of such protection is confounded by its short half-life and hemodynamic effects. We attempted to avoid these problems by injecting adenosine directly into cardiac muscle. We gave four adenosine injections (each 0.15 mL, 5 mg.mL-1 saline) into the left ventricular wall of rat hearts before a 60-minute occlusion. Although infarcts were smaller in adenosine-treated hearts (29 +/- 6%) than in controls (52 +/- 5%; P < .05), injection of saline also reduced infarct size (29 +/- 7%). Infarcts in hearts subjected to needle insertion but no fluid injection differed neither from control nor from fluid-treated hearts (38 +/- 4%). Adenosine reduced ectopic beats and the incidence of ventricular tachycardia during occlusion. In contrast, saline injection prolonged the duration of arrhythmias. To examine the spatial relationship between protection and the injection site, we gave 18 saline injections (each 0.15 mL) into canine myocardium before a 60-minute occlusion. Infarcts were smaller in saline-treated hearts than in controls (P < .01). Because infarcts in four hearts occupied < 3% of the risk region, we concluded that fluid injection did not itself cause appreciable necrosis and speculated that muscle was protected in the vicinity of the injection site. Previous work indicated that muscle can be protected by stretch. We examined this hypothesis by adding gadolinium chloride (a stretch-activated channel blocker) to the saline (0.008 g.mL-1) injection in rat hearts. We again found small infarcts after saline injection (26 +/- 5%); however, gadolinium blocked protection (50 +/- 7%; P < .03). Although we were only partially successful in documenting adenosine-mediated cardioprotection, we found evidence for myocyte protection via a stretch-activated mechanism.

Coronary haemodynamics in left ventricular hypertrophy.

Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. Previous studies have shown that patients with left ventricular hypertrophy develop electrocardiographic changes and left ventricular dysfunction during acute hypotension, and suggest that the lower end of autoregulation may be shifted upwards. To measure coronary blood flow (velocity) and flow reserve during acute hypotension in patients with left ventricular hypertrophy. Eight patients with atypical chest pain and seven with hypertensive left ventricular hypertrophy; all with angiographically normal epicardial vessels. Tertiary referral centre. The physiological range of blood pressure was determined by previous ambulatory monitoring. Left ventricular mass was determined by echocardiography. At cardiac catheterisation, left coronary blood flow velocity was measured using a Judkins style Doppler tipped catheter. During acute hypotension with sodium nitroprusside, coronary blood flow velocity was recorded at rest and during maximal hyperaemia induced by intracoronary injection of adenosine. Quantitative coronary angiography was performed manually. For both groups coronary blood flow velocity remained relatively constant over a range of physiological diastolic blood pressures and showed a steep relation with diastolic blood pressure during maximal hyperaemia with intracoronary adenosine. Absolute coronary blood flow (calculated from quantitative angiographic data), standardised for left ventricular mass, showed reduced flow in the hypertensive group at rest and during maximal vasodilatation. The results are consistent with an inadequate blood supply to the hypertrophied heart, but no upward shift of the lower end of the autoregulatory range was observed.

Effect of Adenosine on Cerebral Blood Flow as Evaluated by Single-Photon Emission Computed Tomography in Normal Subjects and in Patients With Occlusive Carotid Disease

Acetazolamide is commonly used with single-photon CT to assess the cerebrovascular reserve in patients with internal carotid artery stenosis or occlusion. In this study we wanted to evaluate the effects of adenosine, a well-known vasodilatatory compound with a short biological half-life, on brain circulation in humans and compare the results with those of acetazolamide. Acetazolamide (1 g) and adenosine (140 micrograms/kg per minute) were injected intravenously on different days in 6 normal subjects and 6 patients: 4 with unilateral stenosis, 1 with bilateral stenosis, and 1 with complete occlusion of the internal carotid artery. Changes in regional cerebral blood flow relative to that of the cerebellum (cortico/cerebellar ratios) from resting conditions were evaluated by 99mTc-hexamethylpropyleneamine oxime and single-photon emission CT. The measured blood flow ratios increased significantly in the normal group 20 minutes after acetazolamide injection in several cortical and subcortical regions, as well as at the 4th minute of a 6-minute adenosine infusion. Regional cerebral blood flow ratio values were higher after adenosine than after acetazolamide in both cortical (frontal and parietal) and subcortical (thalamus and basal ganglia) regions. In 4 of the 6 patients the side-to-side asymmetry increased from the basal resting condition after the injection of acetazolamide and even more so after the injection of adenosine. Adenosine infusion causes vasodilation of cerebral arteries and can be used for the investigation of cerebrovascular perfusion capacity in patients with carotid occlusive disease. One advantage in the use of adenosine over acetazolamide is the possibility of interrupting the test with reversal of clinical symptoms or patient discomfort within a few minutes.

Lack of a role of adenosine in activation of ischemically sensitive cardiac sympathetic afferents.

Adenosine has been implicated in the pathogenesis of cardiac pain through activation of cardiac sympathetic afferents. The present study was performed to assess directly the contribution of adenosine in activating ischemically sensitive cardiac sympathetic afferents. Single-unit activity of ischemically sensitive afferents located in both ventricles was recorded from the left thoracic sympathetic chain or rami communicantes of anesthetized cats during 5 min of myocardial ischemia. Intracardiac injection (5 mg) or epicardial application (1-5 mg/ml) of adenosine onto the receptive fields failed to activate 31 ischemically sensitive A delta- and C fiber afferents, which were responsive to topical application of bradykinin (10 micrograms/ml). Intracardiac injection (5 mg) or topical application (1-5 mg/ml) of an adenosine A1 receptor agonist, N6-cyclopentyladenosine, also did not increase the discharge activity of 13 other ischemically sensitive C fiber afferents. Treatment with dipyridamole (1 mg/kg iv) to inhibit the cellular uptake of adenosine did not significantly potentiate the response of 10 separate C fiber afferents to 5 min of myocardial ischemia. Furthermore, blockade of adenosine receptors with aminophylline (5 mg/kg iv) did not significantly attenuate the response of 10 other C fiber afferents to 5 min of myocardial ischemia. The results of the present study demonstrate that exogenous and endogenous adenosine do not contribute to activation of ischemically sensitive cardiac sympathetic afferents. The findings of the present study fail to support a substantial role for adenosine and its A1 receptors in activation of cardiac sympathetic afferents during myocardial ischemia.