Maria Iamele

Muscular and cardiac adenosine-induced pain is mediated by A1receptors

OBJECTIVES This study attempted to establish whether bamiphylline, a selective antagonist of A1 adenosine receptors, prevents the algogenic effects of adenosine in humans. BACKGROUND Experimental findings indicate that the sympathoexcitatory response elicited by adenosine is mediated by A1 receptors. METHODS An intrailiac infusion of increasing doses (from 125 to 2,000 micrograms/min) of adenosine was given to 20 patients. Adenosine infusion was then repeated after intrailiac infusion of either bamiphylline or saline solution. In 14 other patients with angina, increasing doses of adenosine (from 108 to 1,728 micrograms/min) were infused into the left coronary artery. Adenosine infusion was then repeated after the intravenous infusion of either bamiphylline or placebo. Coronary blood flow velocity was monitored by a Doppler catheter. Data relative to pain severity are expressed as median and all other data as mean value +/- 1 SD. RESULTS Bamiphylline prolonged the time to pain onset caused by the intrailiac adenosine infusion from 444 +/- 96 to 749 +/- 120 s (p < 0.001) and reduced pain severity from 45 to 24 mm (p < 0.01). After placebo infusion, the time to pain onset and pain severity were similar to that of baseline (428 +/- 112 vs. 430 +/- 104 s, p = 0.87 and 44 vs. 43 mm, p = 0.67, respectively). Bamiphylline prolonged the time to pain onset caused by intracoronary adenosine infusion from 519 +/- 128 to 603 +/- 146 s (p < 0.01) and reduced pain severity from 58 to 28 mm (p < 0.02). After placebo infusion, the time to pain onset and pain severity were similar to that at baseline (542 +/- 87 vs. 551 +/- 79 s, p = 0.14 and 55 vs. 50 mm, p = 0.61). Maximal coronary blood flow velocities before and after bamiphylline administration were similar (47 +/- 22 vs. 49 +/- 24 cm/s, p = 0.36) as well as before and after placebo administrtion (40 +/- 20 vs. 41 +/- 20 cm/s, p = 0.07). CONCLUSIONS Bamiphylline reduces adenosine-induced muscular and cardiac pain but does not affect adenosine-induced coronary vasodilation. These findings indicate that at the dose used in this study, bamiphylline does not detectably block vascular A2-receptor-mediated adenosine effects in humans, which suggests that the muscular and cardiac algogenic effects of adenosine are mediated mainly by A1 receptors.

Analgesic effect of bamiphylline on pain induced by intradermal injection of adenosine

&NA; Adenosine is known to cause pain when injected intravenously or intra‐arterially. We have conducted a double‐blind placebo‐controlled study by injecting adenosine intradermally in 6 healthy subjects (5 male, 1 female; age: 27–34 years). Pain was assessed using the visual analogue scale. The intradermal injection of 2 &mgr;mol of adenosine produced pain significantly greater than normal saline after 15 sec (T0) (29 ± 13 vs. 7 ± 6 mm, P = 0.004), 1 min after T0 (13 ± 9 vs. 0 ± 0 mm, P = 0.002) and 2 min after T0 (4.5 ± 5 vs. 0 ± 0 mm, P < 0.05). There was evidence of hyperalgesia to mechanical and heat stimuli at the injection site (primary hyperalgesia). There was no evidence of mechanical hyperalgesia in the cutaneous area surrounding the injected site (secondary hyperalgesia). In all cases the intradermal injection of adenosine produced local hyperemia (mean surface are: 147 ± 69 mm2) which was absent after placebo injection. The pre‐injection of bamiphylline, a rather selective antagonist of A1 adenosine receptors, differently from placebo, completely suppressed the adenosine‐induced pain after 15 sec (T0) (15 ± 10 vs. 0 ± 0 mm, P = 0.002) and 1 min after T0 (9 ± 7 vs. 0 ± 0 mm, P = 0.002). No anesthesia to heat, cold and mechanical stimuli was detected at the bamiphylline site. The adenosine‐induced erythematous area was wider at the bamiphylline pre‐injected site than at the placebo pre‐injected site (173 ± 114 vs. 119 ± 85 mm2). We conclude that adenosine is an algogenic substance able to activate not only visceral but also cutaneous nociceptors. Furthermore our results suggest that the activation of nociceptors is at least partially mediated by A1 adenosine receptors.

Usefulness of Transcatheter Patent Foramen Ovale Closure in Migraineurs With Moderate to Large Right-to-Left Shunt and Instrumental Evidence of Cerebrovascular Damage

Transcatheter patent foramen ovale (PFO) closure might be effective in improving migraines. To assess the efficacy of PFO closure in migraineurs with a moderate to large right-to-left shunt and instrumental evidence of embolic cerebral damage, 76 highly symptomatic migraineurs were prospectively investigated. The presenting clinical syndrome was stroke in 16 patients, repeated transient ischemic attack in 32 patients, and lone migraine associated with cerebral ischemic lesions on magnetic resonance imaging in 28 patients. Migraine severity was assessed before PFO closure and monthly for 6 months after discontinuation of antiplatelet therapy. At the end of 12 months of follow-up, the averaged postprocedural total score was compared with the baseline score. Transcatheter PFO closure was successful in all patients, and the 12-month PFO closure rate was 97%. The baseline total migraine score was similar in patients with stroke, transient ischemic attack, and lone migraine (6.8 +/- 1.6, 6.7 +/- 1.4, and 6.9 +/- 1.7 respectively, p = NS). After a mean follow-up of 13.7 +/- 2.4 months, no recurrent cerebrovascular episodes had occurred. At the end of the follow-up period, a significant reduction in the total migraine score was observed in all groups, regardless of the initial clinical presentation. Migraine was completely abolished in 35 patients (46%), improved in 27 (36%), and unchanged in 14 (18%). The proportion of patients with migraine suppression and improvement was similar in the 3 groups. In conclusion, in highly symptomatic migraineurs with previous ischemic cerebral events and instrumental evidence of cerebral embolism, transcatheter PFO closure can result in improvement of migraine severity in a high percentage of patients.

Substance P potentiates the algogenic effects of intraarterial infusion of adenosine

OBJECTIVES This study investigated whether substance P potentiates the muscular and cardiac pain caused by the intraarterial infusion of adenosine, an autocoid known to induce muscular and cardiac ischemic-like pain in humans. BACKGROUND Substance P is involved in the generation of neurogenic inflammation and causes cutaneous hyperalgesia. Because substance P is present in perivascular nerves it might also cause muscular and cardiac hyperalgesia. To test this hypothesis its effects on adenosine-induced muscular and cardiac pain were investigated in humans. METHODS A randomized, crossover study of the algogenic effects of the intrailiac infusion of increasing scalar doses (from 125 to 2,000 micrograms/min) of adenosine or substance P (11.2 pmol/min) for 3 min, followed by the simultaneous infusion of substance P plus the same doses of adenosine, was carried out in nine patients with no evidence of peripheral vascular disease. A similar protocol was carried out by infusing increasing scalar doses of adenosine (from 50 to 800 micrograms/min) or substance P (11.2 pmol/min) for 3 min, followed by the simultaneous infusion of substance P plus the same doses of adenosine, into the left coronary artery of eight patients with angina. Pain severity, assessed by a visual analog scale, is presented as median. The remaining data are presented as mean value +/- 1 SD. RESULTS All patients experienced pain during both adenosine and substance P plus adenosine infusion; no patient experienced pain during the infusion of substance P alone. During intrailiac infusion, all patients experienced pain in the right leg that occurred earlier (207 +/- 152 vs. 321 +/- 154 s, p < 0.05) and was greater (47 vs. 30 mm, p < 0.05) during the simultaneous infusion of substance P plus adenosine than during the infusion of adenosine. Similarly, during intracoronary infusion, all patients experienced chest pain that occurred earlier (409 +/- 242 vs. 596 +/- 210 s, p < 0.05) and was greater (51 vs. 33 mm, p < 0.05) during the simultaneous infusion of substance P plus adenosine than during infusion of adenosine. No patient exhibited electrocardiographic signs of ischemia. CONCLUSIONS Substance P does not cause muscular or cardiac pain, but it provokes muscular and cardiac hyperalgesia.

Risk factors in schoolchildren associated with a family history of unheralded myocardial infarction or uncomplicated stable angina in male relatives.

OBJECTIVES The aim of this study was to compare risk factors for coronary atherosclerosis in children with a family history of unheralded myocardial infarction or uncomplicated stable angina. BACKGROUND In patients with unheralded myocardial infarction, coronary atherosclerosis might have a greater tendency to cause acute coronary occlusion than in patients with uncomplicated stable angina, suggesting the possibility of different risk factors in these two groups of patients. METHODS Serum lipid levels were compared in children with a family history of unheralded myocardial infarction (236 children) or uncomplicated stable angina (48 children) or no family history of ischemic heart disease (613 children). RESULTS Mean (+/- 1 SD) total serum cholesterol was higher in children with a family history of myocardial infarction than in control subjects (161 +/- 28 vs. 154 +/- 25 mg%, p < 0.01). In children with a family history of stable angina, mean total serum cholesterol (159 +/- 25 mg%) was similar to that in children with family history of myocardial infarction. High density lipoprotein cholesterol and apolipoprotein A-I were higher in children with family history of stable angina than in children with family history of myocardial infarction and control subjects (69 +/- 18 vs. 61 +/- 13 and 60 +/- 13 mg%, p < 0.01; 143 +/- 23 vs. 130 +/- 18 and 129 +/- 18 mg%, p < 0.01, respectively). In children with a family history of myocardial infarction, the low density/high density lipoprotein cholesterol ratio was significantly higher than in control subjects (1.53 +/- 0.64 vs. 1.44 +/- 0.56, p < 0.05). Conversely, in children with a family history of stable angina, this ratio (1.24 +/- 0.51) was significantly lower (p < 0.05) than in control subjects. CONCLUSIONS Risk factors for coronary athersclerosis in children with a family history of unheralded myocardial infarction are different from those in children with a family history of uncomplicated stable angina. Higher levels of apolipoprotein A-I early in life might reduce the risk of acute coronary syndromes.

Feasibility and safety of transcatheter closure of atrial septal defects with deficient posterior rim.

To evaluate the feasibility and safety of percutaneous closure of complex secundum‐type atrial septal defects (ASD) in patients with posterior‐inferior rim deficiency.

Effect of Percutaneous Closure of Patent Foramen Ovale on Post-Procedural Arrhythmias

To the Editor: Atrial arrhythmias after percutaneous patent foramen ovale (PFO) closure, including atrial fibrillation (AF), has been consistently reported in different series suggesting a causal link between mechanical closure of PFO and the new onset of post-procedural arrhythmias [(1–3)][1].

AMPLATZER versus Figulla occluder for transcatheter patent foramen ovale closure

AIMS The aim of this observational study was to compare acute and 12-month results of percutaneous closure of patent foramen ovale (PFO) with two occluder devices. METHODS AND RESULTS Between June 2007 and October 2014, 406 consecutive patients (48.1±13.3 years, 243 women) underwent percutaneous PFO closure with either the AMPLATZER (n=179) or the Figulla (n=227) device after a stroke or a transient ischaemic attack ascribed to the PFO. A right-to-left shunt grade >1 was previously detected in all patients and atrial septal aneurysm was present in 111 (27.5%) patients. Patients were followed up with a contrast transthoracic echocardiogram and clinically at 24 hours, six months, and 12 months after the procedure. A high procedural success was observed in both groups. Despite a trend towards a higher incidence of acute residual shunt immediately after device deployment among Figulla occluder patients, a residual grade ≥2 right-to-left shunt was observed in 4.5% of patients, independently of the device used for PFO closure. The only difference reported after Figulla device implantation was a lower rate of supraventricular arrhythmias (9% vs. 17%, p=0.02). CONCLUSIONS According to this two-centre study, PFO closure appears safe and effective with the Figulla occluder as well as with the AMPLATZER device.

Very late patent foramen ovale occluder device embolization.

A 36-year-old woman with a decade-long history of repeated transient ischemic attacks and disabling migraine was referred to our center for patent foramen ovale (PFO) assessment. Magnetic resonance scan showed bilateral cerebral lesions and transthoracic echocardiography (TTE) with microbubble test confirmed the presence of a wide PFO with massive basal rightto-left shunt. Transesophageal echocardiography (TEE) revealed a mobile septum primum with 11 mm maximal excursion with a base span of 20 mm. On the basis of clinical and instrumental data, the patient underwent percutaneous PFO closure. The procedure was carried out under TEE and fluoroscopic monitoring by positioning an Amplatzer Cribriform 25 mm device (AGA Medical, Golden Valley, Minnesota, USA). After vigorous

Single Transseptal Puncture for Left Atrial Appendage Closure and Mitral Valvuloplasty With Total Cerebrovascular Protection in a Patient With Acute Embolic Cerebral Ischemia

A 69-year-old patient with dyspnea and sudden onset of right hemiplegia and dysarthria was admitted to our institution and rapidly underwent successful mechanical thrombectomy because of a basilar artery occlusion. A good functional outcome was achieved. The diagnostic work-up revealed rapid–