Biomedical subjects

M Chiariello

Publications and source records attributed to M Chiariello.

At least 181 records · Page 10Linked to original sources

PubMed1993

[Ablation of paroxysmal tachycardia in Wolff-Parkinson-White syndrome].

Surgical or catheter ablation of accessory pathways by means of high energy shock has been substantial associated with morbidity and mortality. On the contrary radiofrequency current, an alternative energy source for ablation, has a low incidence of complications and a very high success rate. Aim of this study was to relate about the results using catheter ablation of accessory pathways by radiofrequency current in our Electrophysiologic laboratory. Radiofrequency current (20-40 W) was delivered between a large-tip catheter electrode positioned against the mitral or tricuspid anulus and a standard adhesive electrosurgical dispersive pad applied to the left chest wall. When possible radiofrequency delivery was guided by catheter recordings of accessory pathway activation. Ablation was attempted in 181 patients with 191 accessory pathways. We obtained successful ablation of 187/191 accessory pathways and accessory pathway conduction was eliminated in 177/181 patients. During a mean follow-up of 14 +/- 10 months preexcitation returned in 7 patients (3.9%). All underwent a second successful ablation. In 1 patient, during the procedure, we observed a transient ischemic attack, with no complications. In accordance to other reports we conclude that radiofrequency ablation is highly effective in ablating accessory pathways, with low morbidity and no mortality.

Adolescent↗

PubMed1993

[Anti-angina activity of potassium-channel activators].

Recently, a new class of drugs has been developed with unique properties with regard to cardiovascular pharmacology: K(+)-channel openers. The increased K+ efflux from smooth muscle cells induced by these drugs is accompanied by a reduced intracellular availability of free Ca++, which in turn induces vascular relaxation. This property is currently being exploited to achieve peripheral and coronary artery dilatation in patients with ischemic heart disease. Cromakalim, pinacidil, and nicorandil, are the most extensively investigated agents in this class. Nicorandil, in addition to its K(+)-channel opener property, also shows a nitrate-like activity on guanylate cyclase of vascular smooth muscle cells. Clinical trials demonstrate that chronic administration of nicorandil can significantly increase exercise tolerance in patients with coronary artery disease. In experimental studies, this drug has also shown protective effects against myocardial injury induced by ischemia and reperfusion, by mechanisms partly independent of its vasodilating properties. These results suggest that K(+)-channel openers may have a relevant place in the pharmacological treatment of patients with ischemic heart disease.

Angina Pectoris↗

PubMed1993

[A methodological approach to the transcatheter radiofrequency ablation of anomalous Kent-type pathways].

Aim of this study is to suggest our methodological approach for transcatheter ablation of Kent bundles by radiofrequency energy as to the potential ablation sites, the need in unipolar or bipolar recording mode, single catheter or multiple catheters mapping of anomalous pathways, the vascular approach for both left sited and right sited anomalous pathways, and finally the duration and power to supply. The recording of Kent potential and/or a Va-QRS interval > or = 0 ms have been considered significant predictors of success (respectively p < 0.001 and p < 0.05). The unipolar recording mode has been considered critical in the choice of ablation site in 47 (29.9%) patients. A 6-catheter approach for both diagnostic electrophysiologic studies and mapping allowed us to easily localize accessory pathways and to record either a probable or possible Kent potential in a high percentage of patients and to reduce the permanence of the ablation catheter in the left ventricle. By transaortic retrograde approach in ablating left sited anomalous pathways, we obtained a high success rate, while right sited accessory pathway were approached from the inferior vena cava. In right sited anomalous pathway we delivered radiofrequency energy for a longer time in order to avoid a relapse soon after the procedure. We performed ablation of 174/178 (97.7%) anomalous pathways in 165/169 (97.6%) patients. We observed a 3.8% relapse during a mean follow up of 13 +/- 9 months.

Adolescent↗

PubMed1993

[The usefulness of bioimpedance in patient monitoring in an intensive-therapy heart-surgery unit: a comparison with thermodilution].

Haemodynamic monitoring of intensive care unit (ICU) patients can be carried out by thermodilution system. This method is invasive, does not give a continuous monitoring and complications can occur. Thoracic electrical bioimpedance (TB), a non invasive, fast, easily repeatable method, is able to measure some important haemodynamic parameters: end diastolic volume (EDV), stroke volume, cardiac output (CO), ejection fraction (EF), some contractility indexes, systemic vascular resistances (SVR) and cardiac work. The aim of the present study is to compare CO and SVR obtained by thermodilution with the same indexes obtained by TB. Therefore, 20 ICU patients (12 males and 8 females, mean age 54 +/- 11 years) were studied. Out of them, 16 had been submitted to cardiac surgery in the previous 7 days and 4 were waiting for cardiac surgery. The patients were divided in 2 groups: Group A (N 4) included patients with valvular malfunction and/or cardiac arrhythmias and Group B (N 16) included patients with normal valvular function and sinus rhythm. CO obtained by TB was well related with the one obtained by invasive (INV; r = 0.878; p < 0.001). The mean value of difference of the 2 methods was 12.29 +/- 11.83 for the whole group of 20 patients but it was 26.07 +/- 14.16 in the Group A and 8.84 +/- 8.09 in the Group B confirming the less reliability of the method in patients with abnormal valvular function or in the presence of cardiac arrhythmias. As a consequence, SVR obtained by TB and INV resulted well related (r = 0.752; p < 0.001). The mean value of differences was 11.14 +/- 9.01 in the group of 20 patients and particularly 19.55 +/- 10.87 in the Group A and 9.04 +/- 7.07 in the Group B. In a subgroup of 9 patients, CO was measured at successive times (0, 30, 60, 90 min) by both TB and INV; when comparing the 2 CO values a significant correlation was observed. In conclusion, TB represents a valid method in haemodynamic monitoring of the ICU patients.

Adult↗

PubMed1993

Clinical experience with the transvenous Medtronic Pacer Cardioverter Defibrillator (PCD) System.

We review our experience with the transvenous Medtronic Pacer Cardioverter Defibrillator System (Model 7217B), a multifunction implantable pacer defibrillator combined with a transvenous lead system (Transvene). From April 1991 to October 1992, we implanted this device in 19 consecutive patients (11 men and 8 women; average age, 56.5 years). Nine patients (47.4%), 5 with coronary artery disease and 4 with dilated cardiomyopathy, had an ejection fraction of < 30%. The average operative time was 129 minutes. In 18 patients (94.7%), the transvenous lead system provided effective sensing, pacing, and defibrillation during intraoperative testing. In each of these cases, the defibrillation threshold was less than 18 J. In 1 patient (5.3%), it was necessary to switch to epicardial leads, which were implanted through a left thoracotomy. All patients were extubated in the recovery room. The average hospital stay was 8 days. There was no early mortality or morbidity. During a maximum follow-up period of 17 months (mean, 9.2 months), no sudden death occurred. The implantable system terminated 245 ventricular tachycardia episodes in 14 patients (73.7%) and 82 ventricular fibrillation episodes in 13 patients (68.4%). Two hundred eleven (86.1%) of the ventricular tachycardia episodes were resolved by antitachycardia pacing alone. In 2 patients (10.5%), the caval electrode became dislocated; repositioning of the electrode was followed by repeat defibrillation threshold evaluation. Our experience shows that the transvenous Medtronic Pacer Cardioverter Defibrillator System provides safe, effective treatment of ventricular tachyarrhythmias. Because the perioperative mortality and morbidity are extremely low, use of this device may be particularly beneficial in patients with a high operative risk. Moreover, the lower number of unpleasant therapeutic shocks should increase patient a acceptance of the device.

Adult↗

PubMed1993

[The effects of the selective intracoronary administration of nifedipine on left ventricular filling anomalies during coronary angioplasty].

Eighteen patients with isolated stenosis of left anterior descending artery, were randomly given 0.2 mg of nifedipine (Group II) or its solvent (Group I) via balloon catheter positioned across the lesion immediately prior balloon occlusion. Peak velocity of early (E peak) and late (A peak) filling, velocity flow integral at early (E area) and late (A area) filling and their ratios (by echo-Doppler) and heart rate, mean aortic and wedge (W) pressures were measured at baseline, 15 and 30 s during balloon occlusion and 10 min after balloon deflation. In Group I we observed a significant decrease in either E peak at 15 and 30 s (-24.7%, -29.3% respectively) and E area (-32.8%, -40.0% respectively) with a non significant increase in both A peak and A area. Accordingly, either E/A peak ratio and E/A area ratio decreased significantly. In Group II no significant changes were observed in the echo-Doppler parameters of left ventricular filling. Wedge pressure also significantly increased in Group I at 15 and 30 s (68.7% and 97.9% respectively), while a significant increase in Group II occurred only at 30 s (32.5%). Heart rate significantly increased only in Group I at 15 and 30 s (10.3% and 11% respectively), while aortic pressure remained unchanged in both groups. Thus, nifedipine given intracoronary in the post-stenotic area just before balloon occlusion prevents left ventricular filling dynamic alteration by preserving early filling.

Adult↗

PubMed1993

Hibernating and stunned myocardium.

The term "hibernating" myocardium has been introduced to indicate the presence of regional asynergy due to persistent hypoperfusion, which can be reversed after revascularization. The mechanisms underlying the prolonged functional adaptation of myocardial cells to hypoperfusion are still not clear, although preliminary experimental data indicate that a reduced availability of intracellular Ca++ may play an important role. The identification of hibernating myocardium may have therapeutic implications, since it has been demonstrated that the revascularization of hibernating myocardial territories may lead to regional and global improvement of systolic left ventricular function. The noninvasive identification of hibernating myocardium can be accomplished by positron emission tomography, which demonstrates the presence of preserved metabolic activity in hibernating myocardial territories. However, exercise 201thallium scintigraphy, using the reinjection technique, with a quantitative regional analysis of 201thallium uptake, has also been reported to provide information comparable to that obtained by positron emission tomography. "Stunning" of the myocardium indicates a condition of transient impaired regional systolic function, following an episode of ischemia. The mechanisms determining the slow recovery of function after ischemia are still not completely understood. Experimental data suggest in this case a reduced Ca++ affinity of the myofibrils and a reduced maximal calcium-activated force.

Animals↗

PubMed1993

The in vivo antiplatelet effects of thromboxane A2 synthase inhibitors are potentiated by simultaneous thromboxane A2/prostaglandin H2 receptor blockade.

The aim of the present study was twofold: 1) to assess whether inhibition of thromboxane A2 (TxA2) synthase exerts more potent antiplatelet effects when applied concomitantly with TxA2 and prostaglandin (PG)H2 receptor blockade and 2) whether these effects are mediated through redirection of PG endoperoxides toward the synthesis of antiplatelet PGs, such as PGI2 and PGE2. Thus, cyclic flow variations (CFVs), due to recurrent platelet aggregation, were initiated in the stenotic, endothelially injured carotid arteries of 39 rabbits. After 30 min of CFVs, the animals received: 1) SQ29548 (up to 0.6 mg/kg bolus + 0.2 mg kg-1 hr-1, n = 13), a TxA2/PGH2 receptor antagonist; 2) dazoxiben (up to 15 mg/kg bolus + 5 mg kg-1 hr-1, n = 13), a TxA2 synthase inhibitor and 3) picotamide (up to 20 mg/kg bolus + 20 mg kg-1 hr-1, n = 13), a drug with simultaneous TxA2 synthase and receptor blocking properties. CFVs were abolished in 6, 7, and 12 animals treated with SQ29548, dazoxiben, and picotamide, respectively (P < .01 for picotamide versus SQ29548 and dazoxiben). The animals in which CFVs were not abolished by SQ29548 or dazoxiben received the other drug at the same dose. CFVs were abolished by dazoxiben in five of seven rabbits that initially did not respond to SQ29548 and by SQ29548 in five of six animals that did not respond to dazoxiben. All animals that responded to the combination of SQ29548 and dazoxiben, as well as those that responded to picotamide, received increasing intravenous infusions of epinephrine to restore CFVs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

[Coronary vasoconstriction induced by digoxin in normal subjects and in patients with coronary atherosclerosis].

This study evaluated the effects of digoxin infusion (0.014 mg/kg in 10 min i.v.) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (aged 47 +/- 12), divided in 3 groups were studied. The effects of digoxin infusion (after 10 and 20 min) and sublingual administration of isosorbide dinitrate were investigated in Group I (patients with angiographically normal coronary arteries, n = 9) and in Group II (patients with atherosclerotic coronary arteries, n = 8). In Group III (n = 5) to determine whether or not the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiographies were performed after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, i.v.). In Group I, 10 min after the end of digoxin infusion, cross-sectional area decreased from 7.7 +/- 4.1 mm2 to 6.0 +/- 2.2 mm2, and after 20 min to 5.6 +/- 2.6 mm2 (p < 0.05). Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (NS versus baseline). By 20 min after digoxin infusion heart rate was significantly reduced from 79 +/- 16 to 74 +/- 13 b/min (p < 0.01). Peripheral vascular resistances increased significantly 10 min after digoxin infusion (from 1396 +/- 693 to 1693 +/- 984 dyne*s*cm-5, p < 0.05), whereas cardiac output did not change. In Group II, minimal stenosis diameter decreased significantly 20 min after digoxin infusion from 1.6 +/- 0.5 mm to 1.4 +/- 0.5 mm (p < 0.05). Again, isosorbide dinitrate reverted digoxin-induced vasoconstriction as minimal stenosis diameter increased (NS versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Reverse redistribution in resting thallium-201 myocardial scintigraphy in patients with coronary artery disease: relation to coronary anatomy and ventricular function.

We studied 25 male patients, with coronary artery disease, mean age 56 +/- 8 yr. All underwent 201Tl rest-redistribution and resting 99mTc methoxyisobutyl isonitrile (MIBI) cardiac imaging. Regional 201Tl and MIBI uptake were quantitatively analyzed. Regional left ventricular wall motion (WM) was visually assessed on MIBI gated images using a three-point scale (0 = normal, 1 = hypokinetic, 2 = a/dyskinetic). Two patterns of reverse redistribution (RR) were identified: RR-A when 201Tl uptake was normal on rest images and abnormal on redistribution images, and RR-B when 201Tl uptake was abnormal on rest images and a significant decrease in uptake was observed on redistribution images. Of the total 375 myocardial segments analyzed, 229 were classified as normal (Nl), 40 as reversible defect (RD), 74 as irreversible defect (ID); 26 showed RR-A while 6 myocardial segments had RR-B. Myocardial segments with RR-A differed from NI in the degree of coronary artery stenosis (81% +/- 33% versus 57% +/- 39%, respectively, p < 0.05), in WM score (1.1 +/- 0.7 versus 0.5 +/- 0.6, respectively, p < 0.01), and in MIBI uptake (81% +/- 10% versus 92% +/- 9%, respectively, p < 0.0001). Moreover, the percent of myocardial segments supplied by a totally occluded coronary artery was significantly higher (p < 0.05) in myocardial segments with RR-A (46%) than in NI (22%). Segments with RR-B did not show any significant difference either from RD and ID. These results suggest that myocardial segments with RR-A on resting 201Tl images have impaired function and are supplied by severely stenosed coronary arteries and should not be considered normal.

Adult↗

PubMed1992

Experimental carotid stenosis and endothelial injury in the rabbit: an in vivo model to study intravascular platelet aggregation.

Previous studies have shown that experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in coronary flow to almost zero values followed by restorations of flow to normal values. This pattern of flow, called cyclic flow reductions (CFRs), is the consequence of recurrent platelet aggregation at the site of the stenosis and endothelial injury and subsequent dislodgement of the thrombus. In the present study, platelet activation and aggregation in vivo was induced by placing an external constrictor around carotid arteries with endothelial injury in anesthetized rabbits. Carotid blood flow velocity was measured continuously with a Doppler flow probe positioned proximally to the constrictor. After placement of the constrictor, CFRs developed in 14 of 14 rabbits with a mean frequency of 16.5 +/- 2.3 cycles/h. CFRs were observed for 30 min, and the animals were treated with either an i.v. bolus of aspirin (10 mg/kg) or R 68070 (20 mg/kg), a drug with simultaneous TxA2 synthase and TxA2/PGH2 receptor blocking properties. Aspirin completely inhibited CFRs in 4 of 7 rabbits, whereas R 68070 eliminated CFRs in 7 of 7 animals. In the 3 animals that did not respond to aspirin, administration of ketanserin (0.25 mg/kg i.v.), a selective serotonin S2 receptor antagonist, completely abolished CFRs. Both aspirin and R 68070 resulted in a marked reduction in serum TxB2 formation and in a complete inhibition of ex vivo platelet aggregation in response to arachidonic acid, whereas aggregation in response to U46619, a TxA2 mimetic, was inhibited only in R 68070-treated rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Influence of atenolol on the relationship between heart rate and QT interval in patients with exercise-induced myocardial ischemia.

The aim of this study was to analyze the relationship between heart rate and QT interval (HR-QT) during exercise in control subjects (Group A) and in patients with coronary artery disease (CAD) with effort angina and without previous myocardial infarction (MI) (Group B). The diagnosis of CAD was confirmed by coronarographic examination. The correlation HR-QT was significant (p < 0.001) in both groups on effort and at recovery. The analysis of the regression HR-QT was carried out separately, both on effort in upright position and at rest in supine position, to avoid the influence of posture on QT length. During effort, the regression line showed lower slope and intercept values in Group B (p < 0.001) than those for Group A. A similar behavior was also observed at rest. Thus, at the highest heart rate, where ECG signs of ischemia (ST depression > 1 mm) frequently occurred, a longer QT interval was present in Group B. Moreover, in Group B, the QT interval in the presence of ECG signs of ischemia was significantly longer (p < 0.01) than in Group A at comparable heart rates both on effort and at rest, thereby confirming the result obtained by comparing both regression lines. The same effort protocol was repeated in Group B patients after acute administration of atenolol 100 mg per os. After atenolol administration, the analysis of the regression HR-QT in Group B clearly showed a shorter QT interval than that obtained in washout period during the baseline test at the highest heart rates where the ECG frequently showed signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

Comparison between exercise and trans-oesophageal atrial pacing in patients with coronary artery disease: technetium-99m methoxy isobutyl isonitrile simultaneous evaluation of ventricular function and myocardial perfusion.

In this study we compared the results of exercise and trans-oesophageal atrial pacing (TAP) technetium-99m methoxyisobutyl isonitrile (99mTc-SESTAMIBI) cardiac imaging in the evaluation of left ventricular (LV) function and myocardial perfusion in patients with angiographically proven coronary artery disease. Ten patients (8 men and 2 women, mean age 59 +/- 6 years) were submitted to 3 separate injections of 99mTc-SESTAMIBI, one under control conditions, one after exercise and one after TAP. LV ejection fraction, as measured by electrocardiogram (ECG) gated first pass, decreased from 49 +/- 5% under control conditions to 42 +/- 6% during exercise (P less than 0.05 versus control) and to 43 +/- 8% during TAP (P less than 0.05 versus control and insignificant change versus exercise). Segmental myocardial perfusion analysis was performed on a total of 150 myocardial segments. On both exercise and TAP 99mTc-SESTAMIBI studies, 103 segments (69% of the total) were normal, 32 (21%) had reversible, and 15 (10%) irreversible, perfusion defects. Relative regional tracer uptake was not statistically different between exercise and TAP in normal regions (91.1 +/- 9.1% versus 90.7 +/- 8.5%, respectively), in regions with reversible (61.9 +/- 12% versus 62.4 +/- 10.4%, respectively) and irreversible perfusion defects (55.8 +/- 7.8% versus 58.8 +/- 9.5%, respectively). Our results demonstrated that 99mTc-SESTAMIBI TAP cardiac imaging shows similar results to 99mTc-SESTAMIBI exercise myocardial scintigraphy in the assessment of LV function and myocardial perfusion in patients with coronary artery disease.

Cardiac Pacing, Artificial↗

PubMed1992

Follow-up of a respiratory rate modulated pacemaker.

The efficacy of 27 respiration sensitive rate modulated pacemakers (Biorate RDP-3 Biotec) implanted in the left pectoral area was evaluated every 3 months during a mean follow-up period of 29 months (range 10-50 months). Rate modulation function was unchanged other than for three patients in whom the auxiliary leads became displaced. Two implants lost ventricular sensing in this nonprogrammable model. In all but the three patients, Holter monitoring demonstrated pacing rate variation corresponding to daily activity. Stress test duration increased from 8.2 +/- 1.5 minutes (in fixed rate VVI rate) to 12.83 +/- 2.0 minutes (in the VVIR mode) (P less than 0.05). Right arm movement increased the pacing rate by 5 +/- 3 beats/min (NS), while the left arm movement increase was 30 +/- 5 beats/min (P less than 0.05). Mental, arithmetic, and nifedipine tests did not change the rate modulated pacing rate. The system responded to a change in respiratory rate by an increase in stimulation rate. A satisfactory response in sensitivity and velocity was present only with medium-high workloads. Interference with rate modulation occurred with movement of the arm ipsilateral to the implanted pulse generator.

Atrial Fibrillation↗

PubMed1992

Effects of ischemia and reperfusion on cardiac tolerance to oxidative stress.

Oxidative stress may affect cardiac function and metabolism. Oxidants are normally inactivated by reacting with reduced glutathione (GSH), with resulting formation and release of oxidized glutathione (GSSG). However, ischemia might affect glutathione metabolism. This might render ischemic hearts less resistant against subsequent oxidant injury during reperfusion, and it might also affect the reliability of GSSG measurements as a means to investigate oxidative stress in reperfused hearts. We compared the metabolic and functional consequences of an oxidant load in control rabbit hearts and in hearts reperfused after 30 min of normothermic total ischemia. In controls, H2O2 infusion (H2O2; 5-30 microM) induced a dose-dependent stimulation of GSSG release and a progressive impairment of cardiac function. At these doses, H2O2 challenge of postischemic hearts resulted in biochemical and functional changes identical to those observed in controls. Release of lactate dehydrogenase (LDH) and of GSH was negligible, similar in both groups. In additional experiments, infusion of H2O2 at a much higher dose (200 microM) elicited a further increase in GSSG release from both groups, although GSSG concentrations were lower in postischemic hearts. The functional effects of the 200 microM H2O2 infusion were similar in both groups, all hearts showing rapid and irreversible deterioration of function. Occurrence of irreversible cell injury was also manifested by a large release of LDH and GSH to a similar extent in both groups. These data demonstrate that cardiac tolerance toward oxidants is largely unaffected by a relatively brief episode of severe ischemia and indicate that GSSG release can be reliably used to investigate oxidative stress in reperfused hearts.

Animals↗

PubMed1992

Role of alpha 2-adrenoceptors in normal and atherosclerotic human coronary circulation.

BACKGROUND: Experimental studies on the effects of alpha 2-adrenoceptors on regional coronary blood flow in normal and ischemic myocardium are highly controversial. A beneficial effect on regional ischemic myocardium has been demonstrated in different animal preparations with either alpha 2-adrenoceptor blockade or stimulation. Animal studies also demonstrated that postsynaptic alpha 2-adrenoceptors mediate vasoconstriction in coronary and femoral vascular beds. The aims of the study were 1) to investigate the effects of regional alpha 2-adrenoceptor stimulation on regional coronary blood flow in subjects with angiographically normal coronary arteries, 2) to assess the effect of alpha 2-adrenoceptor blockade on coronary circulation in control subjects, and 3) to examine the influence of atherosclerosis on coronary blood flow response to alpha 2-adrenoceptor blockade. METHODS AND RESULTS: The effect of regional administration of BHT 933 (a selective alpha 2-adrenoceptor agonist) was studied in eight subjects with angiographically normal coronary arteries. The coronary blood flow velocity was measured using a subselective intracoronary 3F Doppler catheter and coronary diameter by quantitative coronary angiography. BHT 933 induced a reduction in coronary artery diameter from 2.5 +/- 0.6 mm to 1.8 +/- 0.4 mm (p less than 0.05) as well as in coronary blood flow velocity (from 6.4 +/- 0.9 cm/sec to 4.6 +/- 1.9 cm/sec, p less than 0.01). In some subjects, ST segment abnormalities occurred. In patients with angiographically normal coronary arteries (n = 6), the regional infusion of a selective alpha 2-adrenoceptor blocking agent after beta-blockade did not change coronary diameter or coronary blood flow velocity. In contrast, in patients with significant coronary stenoses (n = 6), regional infusion of an alpha 2-adrenoceptor blocking agent reduced regional coronary artery diameter (from 2.3 +/- 0.5 mm to 2.1 +/- 0.6 mm, p less than 0.01) as well as coronary blood flow velocity (from 5.8 +/- 0.8 cm/sec to 3.7 +/- 0.6 cm/sec, p less than 0.05); in addition, alpha 2-adrenoceptor blockade significantly increased coronary sinus plasma norepinephrine levels (from 300 +/- 144 pg/ml to 429 +/- 207 pg/ml, p less than 0.01). CONCLUSIONS: The selective in vivo stimulation of alpha 2-adrenoceptors produces a reduction in coronary blood flow and diameter in humans with angiographically normal coronary arteries. alpha 2-Adrenergic blockade does not change coronary blood flow in subjects with angiographically normal coronary arteries (suggesting no resting alpha 2-adrenergic vasoconstrictor tone), whereas in patients with coronary artery stenosis, regional coronary blood flow decreases after alpha 2-receptor blockade. Finally, our data also suggest that alpha 2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the human heart.

Adrenergic alpha-Agonists↗

PubMed1992

Endothelium-derived relaxing factor modulates platelet aggregation in an in vivo model of recurrent platelet activation.

It has been shown that endothelium-derived relaxing factor (EDRF) may inhibit platelet aggregation in vitro through activation of platelet-soluble guanylate cyclase. To assess whether EDRF may also affect platelet function in vivo, intravascular platelet aggregation was initiated by placing an external constrictor around endothelially injured rabbit carotid arteries. Carotid blood flow velocity was measured continuously by a Doppler flow probe placed proximal to the constrictor. After placement of the constrictor, cyclic flow reductions (CFRs), due to recurrent platelet aggregation, developed at the site of the stenosis. After CFRs were observed for 30 minutes, a solution of authentic nitric oxide (NO, n = 10) was infused into the carotid artery via a small catheter placed proximally to the stenosis. Before infusion of NO, CFR frequency averaged 18.3 +/- 2.9 cycles per hour, and CFR severity (lowest carotid blood flow as percentage of baseline values) was 6 +/- 1%. NO completely inhibited CFRs in all animals, as shown by the normal and constant pattern of carotid blood flow (CFR frequency, 0 cycles per hour, p < 0.001; carotid blood flow, 92 +/- 5%, p = NS versus baseline). These effects were transient; CFRs were restored spontaneously within 10 minutes after cessation of NO infusion. After CFRs returned, S-nitroso-cysteine (S-NO-cys), a proposed form of EDRF, was infused into the carotid artery. S-NO-cys also abolished CFRs in all animals but at a significantly lower dose than NO (0.3 +/- 0.1 versus 12 +/- 4 nmol/min). The role of endogenously released EDRF in modulating in vivo platelet function was then tested in additional experiments. In 10 animals, endogenous release of EDRF was stimulated by infusing acetylcholine into the aortic root during CFRs. Infusion of acetylcholine was also associated with a complete inhibition of CFRs, similar to that observed during exogenous infusion of NO or S-NO-cys. These antithrombotic effects of acetylcholine were completely lost when EDRF synthesis was prevented by administration of the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). Furthermore, in six additional rabbits the basal release of EDRF was blocked by L-NMMA after CFRs had been previously abolished with aspirin or the combination of aspirin and ketanserin, a serotonin S2 receptor antagonist. L-NMMA caused restoration of CFRs in all animals, indicating that even the basal release of EDRF is important in modulating platelet reactivity in vivo. Taken together, the data of the present study demonstrate that endogenous EDRF might importantly contribute to the modulation of platelet function in vivo.

Acetylcholine↗

PubMed1992

Diagnosis of coronary artery disease with Tc 99m-methoxy isobutyl isonitrile and transesophageal pacing.

Recently the use of a new radioactive agent with physical and biological properties more favorable than those of thallium 201, methoxy-isobutyl-isonitrile (MIBI) labeled with technetium 99m (Tc 99m), has permitted simultaneous performance of perfusion and function studies in ischemic cardiopathy. Transesophageal atrial pacing (TAP) technique has evolved as an alternative provocative test of ischemia. The authors compared the capability of Tc 99m-MIBI myocardial scintigraphy, combined with TAP, with that of Tc 99m-MIBI, combined with maximal stress test, in the diagnosis of ischemic cardiopathy. They studied 11 patients with a clinical history of angina pectoris. Myocardial scintigraphy was performed at rest, after stress test, and after TAP. Finally, all the patients underwent coronary angiography. The analysis of myocardial perfusion images on both Tc 99m-MIBI associated with TAP and with stress demonstrated, in 165 myocardial segments examined: 143 normal, 20 reversible defects, 2 irreversible defects. The concordance of localization between coronarographic data and scintigraphic reversible and irreversible defects was 85%. In conclusion TAP proves to be a valid and sensitive provocative test of ischemia when combined with myocardial scintigraphy and with Tc 99m-MIBI.

Cardiac Pacing, Artificial↗