Left ventricular hypercontractility and ST segment depression in patients with syndrome X.

OBJECTIVES: This study was designed to assess the relation between rest left ventricular function and exercise capacity in patients with syndrome X. BACKGROUND: Clinical observation has suggested that some patients with syndrome X have a high rest left ventricular ejection fraction. In this study we determined the relation between left ventricular ejection fraction and exercise capacity and the electrocardiographic (ECG) changes that develop on exercise. METHODS: The pattern of left ventricular function, exercise capacity and 24-h ambulatory ECG monitoring were studied in 37 patients (9 men, 28 women; mean age 52 +/- 7 years) with syndrome X (angina with normal coronary arteries and a positive exercise test result). All patients had normal findings on echocardiogram and rest ECG. All treatment was discontinued for > or = 48 h. Left ventricular ejection fraction was determined by computerized analysis of the left ventricular angiogram. In patients with syndrome X, exercise duration and heart rate were measured at 1-mm ST segment depression and at peak exercise. RESULTS: Left ventricular hypercontractility (ejection fraction > or = 80%) was observed in 12 patients (32%) (group 1), whereas 25 patients (68%) had normal left ventricular contraction (group 2). The time to 1-mm ST depression on exercise testing was significantly earlier in group 1 than in group 2 (5.13 +/- 1.03 vs. 10.76 +/- 0.63 min, respectively, p < 0.001). The magnitude of the ST segment depression at peak exercise was significantly greater in group 1 than in group 2 (2.03 +/- 0.2 vs. 1.33 +/- 0.05 mm, respectively, p < 0.001). The mean time for ST segment depression to normalize was significantly greater in group 1 than in group 2 (4.76 +/- 0.78 vs. 3.16 +/- 0.39 min, respectively, p < 0.05). Linear regression analysis of all patients with syndrome X showed a significant correlation between exercise duration and ejection fraction (r = 0.55, p < 0.001). The mean circadian variation of heart rate and episodes of ST segment depression on 24-h ambulatory ECG monitoring were similar in the two groups of patients. CONCLUSIONS: These findings indicate that approximately one third of patients with chest pain, normal coronary angiograms and a positive exercise test have left ventricular hypercontractility, and this is associated with the development of ST segment depression at a lower heart rate and work load and a longer time to normalization of ST segment depression after exercise.

Delayed recovery of coronary resistive vessel function after coronary angioplasty.

OBJECTIVES: The aim of this study was to use Doppler catheterization and sequential dynamic positron emission tomography (PET) to investigate the role and time course of abnormal coronary resistive vessel function in the impairment of the coronary vasodilator response (maximal/basal coronary blood flow) after successful coronary angioplasty. BACKGROUND: The coronary vasodilator response may be impaired immediately after coronary angioplasty, despite successful dilation of a flow-limiting stenosis. METHODS: Twelve men (mean age 52 +/- 10 years) with single-vessel coronary artery disease and normal left ventricular function were studied. The coronary vasodilator response to intravenous dipyridamole (0.5 mg.kg-1 over 4 min) was determined from intracoronary Doppler measurement of coronary flow velocity, before and after successful angioplasty. Basal and maximal myocardial blood flow in the angioplasty region and a normal region were determined in nine patients wtih positron emission tomography with H2(15)0 at 1 day (PET1), 7 days (PET2) and 3 months (PET3) after angioplasty. RESULTS: The coronary vasodilator response, measured by Doppler catheterization, was similar before and immediately after angioplasty, 1.63 +/- 0.41 and 1.62 +/- 0.55, respectively (p = NS). After angioplasty, in seven of nine patients without restenosis, basal myocardial blood flow at PET1, PET2 and PET3 was 0.98 +/- 0.16, 0.94 +/- 0.09 and 0.99 +/- 0.13 ml.min-1 x g-1, respectively, in the remote region and 1.19 +/- 0.23 (p < 0.01 vs. remote region), 1.17 +/- 0.19 (p < 0.01 vs. remote region) and 1.10 +/- 0.08 ml.min-1 x g-1 (p = NS vs. remote region), respectively, in the angioplasty region. Myocardial blood flow after dipyridamole at PET1, PET2 and PET3 was 3.04 +/- 0.68, 3.00 +/- 0.71 and 3.00 +/- 0.60 ml.min-1 x g-1, respectively, in the remote region and 2.11 +/- 0.80 (p < 0.01 vs. remote region), 2.28 +/- 0.73 (p = NS vs. remote region) and 3.06 +/- 0.86 ml.min-1 x g-1 (p = NS vs. remote region), respectively, in the angioplasty region. The coronary vasodilator response at PET1, PET2 and PET3 was 3.15 +/- 0.85, 3.18 +/- 0.68 and 3.08 +/- 0.75, respectively, in the remote region and 1.80 +/- 0.68 (p < 0.01 vs. remote region), 1.94 +/- 0.49 (p < 0.01 vs. remote region) and 2.77 +/- 0.74 (p = NS vs. remote region), respectively, in the angioplasty region. CONCLUSIONS: After successful angioplasty, basal myocardial blood flow is increased for > or = 7 days in the angioplasty region, with a reduction in the dipyridamole-induced increase in maximal myocardial blood flow for > or = 24 h after the procedure. Thus, the coronary vasodilator response is impaired for > or = 7 days after angioplasty, indicating that there is abnormal resistive vessel function in the coronary vascular bed distal to a coronary artery stenosis that persists for 7 days to 3 months.

Diffuse reduction of myocardial beta-adrenoceptors in hypertrophic cardiomyopathy: a study with positron emission tomography.

OBJECTIVES: This study was conducted to determine the myocardial beta-adrenoceptor density as a marker of sympathetic function in patients with hypertrophic cardiomyopathy and normal control subjects. BACKGROUND: Although some cases of hypertrophic cardiomyopathy are familial with an autosomal dominant pattern of inheritance, there remains a substantial proportion of cases in which neither a family history nor genetic abnormalities can be demonstrated. Additional abnormalities, both genetic and acquired, may be important in the phenotypic expression of this condition. Clinical features of the disease and metabolic studies suggest an increased activity of the sympathetic nervous system. METHODS: Eleven patients with hypertrophic cardiomyopathy, none of whom had previously received beta-blocking drugs, and eight normal control subjects underwent positron emission tomography to evaluate regional left ventricular beta-adrenoceptor density and myocardial blood flow using carbon-11-labeled CGP 12177 and oxygen-15-labeled water as tracers. Plasma catecholamines were also measured. RESULTS: Mean (+/- SD) myocardial beta-adrenoceptor density was significantly less in the hypertrophic cardiomyopathy group than in the control group (7.70 +/- 1.86 vs. 11.50 +/- 2.18 pmol/g tissue, p < 0.001). Myocardial blood flow was similar in both groups (0.91 +/- 0.22 vs. 0.91 +/- 0.21 ml/min per g, p = NS). The distribution of beta-adrenoceptor density was uniform throughout the left ventricle in both groups. In the hypertrophic cardiomyopathy group, there was no correlation between regional wall thickness and myocardial beta-adrenoceptor density. There were no significant differences in either plasma norepinephrine or epinephrine concentrations between the two groups. CONCLUSIONS: There is a diffuse reduction in myocardial beta-adrenoceptor density in patients with hypertrophic cardiomyopathy in the absence of significantly elevated circulating catecholamine concentrations. This most likely reflects downregulation of myocardial beta-adrenoceptors secondary to increased myocardial concentrations of norepinephrine and is consistent with the hypothesis that cardiac sympathetic drive is increased in this condition.

Altered resistive vessel function after coronary angioplasty is not due to reduced production of nitric oxide.

BACKGROUND: The coronary vasodilator reserve with dipyridamole may be impaired immediately after successful angioplasty due to reduced endothelial production or release of nitric oxide. As the vasodilator response to exogenous nitrates is enhanced by endothelium removal or inhibition of nitric oxide synthesis, an increased vasodilator response to nitrovasodilators, such as nitroprusside, should occur. METHODS: The coronary vasodilator reserve (maximal/basel coronary blood flow) with intravenous dipyridamole (0.56 mg/min for 4 min) was measured by Doppler catheterization before and after angioplasty in 10 patients with single-vessel coronary disease. At peak dipyridamole effect, incremental doses of nitroprusside (4-50 micrograms/min) were given intracoronary until systolic blood pressure fell by > or = 5 mmHg. RESULTS: Before angioplasty, the coronary blood flow increased from 19.7 +/- 6.1 (mean +/- s.d.) at basal to 30.1 +/- 11.9 ml/min at the peak dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve of 1.62 +/- 0.39 (range 1.20 - 1.96). After angioplasty, the coronary blood flow increased from 32.4 +/- 13.2 at basal to 53.4 +/- 23.3 ml/min at the peak dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve of 1.77 +/- 0.64 (range 1.7-2.42). Sodium nitroprusside had no additional effect on coronary flow (49.5 +/- 20.4 and 52.2 +/- 18.0 ml/min) before and after a fall in systolic blood pressure, respectively. CONCLUSIONS: The vasodilator response to dipyridamole was markedly impaired immediately after successful angioplasty, and was not augmented by intracoronary nitroprusside. Thus, a reduced production or release of nitric oxide in the coronary circulation does not seem to be responsible for the impaired vasodilator response after angioplasty.

Differential nitric oxide synthase activity in ischemic and idiopathic dilated cardiomyopathy.

We measured plasma nitrite and interleukin 1beta levels in patients with idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, and in normal controls. Nitrite levels were abnormally high in both ischemic and idiopathic dilated cardiomyopathy, suggesting increased nitric oxide activity in these conditions.

Ablation therapy for cardiac arrhythmias.

Ablation has become an important and, in some cases, the first-line therapy for a number of tachyarrhythmias. The feasibility of treating arrhythmias with ablation was initially demonstrated with surgical ablation techniques. Recently, catheter ablation techniques have replaced the surgical approach in nearly all cases. Catheter ablation is highly effective for the Wolff-Parkinson-White syndrome, atrioventricular nodal reentry, and atrial ectopic tachycardia. It is effective for atrial flutter, although approximately one quarter of patients treated with catheter ablation continue to require therapy for concomitant atrial fibrillation. The surgical maze procedure has proved to be feasible for preventing atrial fibrillation. The risks and long-term efficacy of catheter ablation maze procedures for atrial fibrillation need to be defined. The efficacy of ablation for ventricular tachycardia varies with the type of tachycardia. Catheter ablation is very effective for the rare idiopathic ventricular tachycardias that occur in structurally normal hearts and for bundle-branch reentry ventricular tachycardia, which occurs most frequently in patients with dilated cardiomyopathy. When performed at an experienced center, surgical ablation is an excellent option for selected patients with ventricular tachycardia due to prior myocardial infarction who have a discrete aneurysm but otherwise well-preserved ventricular function. Catheter ablation shows promise for this arrhythmia, but it can be offered only to those patients who have relatively slow tachycardias that allow catheter mapping. Substantial advances in mapping and ablation technology will continue to occur, allowing nonpharmacologic control of cardiac arrhythmias to be achieved in an ever greater number of patients.

Recipient-to-donor atrioatrial conduction after orthotopic heart transplantation: surface electrocardiographic features and estimated prevalence.

Recipient-to-donor atrioatrial conduction across a suture line has been rarely reported after orthotopic heart transplantation. The relation of such conduction to symptomatic arrhythmias and its prevalence are not known. Recipient-to-donor atrioatrial conduction was demonstrated in a 28-year-old woman with paroxysmal supraventricular tachycardia 7 years after orthotopic heart transplantation. Atrial tachycardia in the recipient atria conducted 2:1 to the donor atria and was eliminated by radiofrequency catheter ablation of a left-sided atrioatrial electrical connection. The electrocardiogram at rest and during exercise, recorded before ablation of the recipient-to-donor connection, showed frequent atrial premature complexes, with variable coupling to the preceding sinus beats, and a change in P-wave morphology during exercise, which reverted to normal during the recovery period. These findings were eliminated by ablation of the recipient-to-donor connection. To determine the prevalence of recipient-to-donor atrioatrial conduction late after transplantation, we evaluated the exercise electrocardiograms of 50 subjects > 5 years after heart transplantation for these features of recipient-to-donor conduction. At least 1 feature was present in 5 subjects, and both were present in 1 subject. Electrical conduction can occur across surgical suture lines in the atria. Recipient-to-donor atrioatrial conduction may occur in < or = 10% of patients late after heart transplantation. It is a potential cause of arrhythmias that can be effectively treated with radiofrequency catheter ablation.

In vivo quantification of pulmonary beta-adrenoceptor density in humans with (S)-[11C]CGP-12177 and PET.

The in vivo regional distribution of pulmonary beta-adrenoceptors was imaged and quantified in humans with the hydrophilic beta-adrenoceptor antagonist (S)-CGP-12177 labeled with carbon-11 [(S)-[11C]CGP-12177] and positron emission tomography (PET). Six normal male volunteers and eight patients with hypertrophic cardiomyopathy were studied. PET scanning consisted of transmission (tissue density), C15O (blood volume), and (S)-[11C]CGP-12177 (beta-adrenoceptor) emission scans. High-specific-activity (S)-[11C]-CGP-12177 (7.1 +/- 2.0 micrograms, 6.5 +/- 2.1 GBq/mumol) was given intravenously followed by a low-specific-activity (S)-[11C]CGP-12177 injection (34.0 +/- 4.8 micrograms, 2.3 +/- 0.8 GBq/mumol). Binding capacity (Bmax) was calculated in each region of interest as picomoles per gram by normalizing it to the local extravascular tissue density. In normal subjects, average Bmax for all regions of interest was 14.8 +/- 1.6 (SD) pmol/g, which is similar to previously reported in vitro values. In both groups there were no differences in beta-adrenoceptor density between peripheral and central regions nor between right and left lungs. In patients with hypertrophic cardiomyopathy, extravascular tissue density was 24% higher than in normal subjects; Bmax per milliliter thoracic volume was correspondingly higher but was not different from that in normal subjects when expressed per gram tissue (15.8 +/- 2.6 pmol/g). These data suggest that in vivo beta-adrenoceptor density may be quantifiable in humans with the use of PET. This should offer a means to study physiological regulation through repeat measurements.

Variable coronary vasomotor responses to acetylcholine in patients with normal coronary arteriograms: evidence for localised endothelial dysfunction.

OBJECTIVE: The vasomotor responses of the epicardial coronary arteries to acetylcholine were examined in patients with normal coronary arteries and chest pain. DESIGN: Quantitative angiography was used to measure minimum lumen diameter of proximal and distal coronary artery segments at baseline, during intracoronary infusion of acetylcholine (10(-7) - 10(-3) mol/l), and following an intracoronary bolus (2 mg) of isosorbide dinitrate. PATIENTS: Coronary arteriograms were obtained in 15 patients (mean (SEM) age 48 (10) years) with normal coronary arteries and chest pain. MAIN RESULTS: In response to the low concentrations of acetylcholine (10(-7) - 10(-6) mol/1) 20 (61%) distal and 11 (41%) proximal segments showed dilatation (group 1), whereas 13 (39%) distal segments and 14 (52%) proximal segments showed constriction (group 2) (P < 0.05 v group 1). In group 1, the maximum dilatation induced by acetylcholine in the proximal and distal segments was 7.83 (1.19)% and 11.6 (2.2)% respectively. In group 2, the maximum constriction at higher concentration was 16.55 (3.3)% and 33.11 (11.63)% in the proximal and distal segments respectively. The two different patterns of the vasomotor response coexisted in eight (53%) of the 15 patients. Intracoronary isosorbide dinitrate caused a greater increase in the coronary luminal diameter of distal segments than in proximal segments in group 1 (25.63 (5.16)% v 12.43 (3.48)%, P < 0.01) but not in group 2 (12.65 (2.53)% v 10.82 (3.33)%. CONCLUSIONS: Constriction and dilatation may occur in proximal and distal coronary artery segments, suggesting local areas of endothelial dysfunction, in response to acetylcholine in patients with chest pain and angiographically normal coronary arteries.

Myocardial beta adrenoceptors and left ventricular function in hypertrophic cardiomyopathy.

OBJECTIVE: To assess the relation between left ventricular function and myocardial beta adrenoceptor density. METHODS: 17 patients with hypertrophic cardiomyopathy, six with and 11 without heart failure, were studied. Left ventricular function was assessed by echocardiography, and myocardial beta adrenoceptors by positron emission tomography. Patient data were compared with those obtained in normal controls. RESULTS: Myocardial beta adrenoceptor density in the 17 patients was 7.00 (SD 1.90) pmol/g v 11.50 (2.18) pmol/g in normal controls (P < 0.01). beta Adrenoceptor density in the six patients with left ventricular failure was 5.61 (0.88) pmol/g v 7.71 (1.86) pmol/g in the 11 patients with normal ventricular function (P < 0.05), and there was a significant correlation (r = 0.52; P < 0.05) between left ventricular fractional shortening and myocardial beta adrenoceptor density. A positive correlation (r = 0.51; P < 0.05) was also found between myocardial beta adrenoceptor density and the E/A transmitral flow ratio, an index of left ventricular diastolic function. CONCLUSIONS: There is myocardial beta adrenoceptor downregulation in patients with hypertrophic cardiomyopathy with or without signs of heart failure.

Phorbol ester enhances activation of adenylate cyclase in bovine aortic endothelial cells.

Endothelial cells possess beta-adrenoceptors linked to adenylate cyclase which may regulate several aspects of endothelial cell function. The potential for this second messenger system to be modulated by protein kinase C activity was investigated. Bovine aortic endothelial cells (BAECs) were cultured in the absence or presence of phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C. Basal and forskolin-, sodium fluoride (NaF)-, and isoproterenol-stimulated adenylate cyclase activity was measured in homogenates from BAECs. beta-adrenoceptor density on membranes from BAECs was measured by 125I-iodocyanopindolol binding. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of immunoprecipitated proteins was used to identify phosphorylated proteins. Pretreatment of BAECs with 100 nM PMA for 30 min increased basal adenylate cyclase activity above control levels, and also increased enzyme activity stimulated by forskolin, NaF, or isoproterenol. Pretreatment of BAECs for 60 min with 100 nM staurosporine, an inhibitor of protein kinase C, prevented the enhancement of adenylate cyclase activity caused by PMA. Treatment of BAECs with PMA did not trigger phosphorylation of the inhibitory guanine nucleotide-binding protein, and there was no change in BAEC beta-adrenoceptor density following PMA pretreatment. Exposure of BAECs to ATP or bradykinin did not mimic the effects of phorbol ester. In conclusion, activation of protein kinase C by PMA enhanced adenylate cyclase activity in BAECs. However, ATP and bradykinin which activate endothelial cell surface receptors linked to phospholipase C did not mimic this effect.

Ventricular tachycardia: an unusual pacemaker-mediated tachycardia.

A 74 year old man had recurrent ventricular tachycardia, which was well controlled with amiodarone, and complete heart block for which a VVI permanent pacing system had previously been implanted. After an elective increase in the programmed pacemaker rate from 70 to 82 beats/min, there was recurrence of frequent episodes of ventricular tachycardia. Each episode of tachycardia was initiated by a fusion beat consisting of a ventricular extrasystole and a paced beat. When the pacemaker rate was reprogrammed to 70 beats/min the episodes of tachycardia ceased abruptly. It is proposed that the fusion of a ventricular extrasystole with a pacemaker beat may have induced ventricular tachycardia, even though neither of these beats occurring separately was sufficient to cause this.

Effects of inhibition of nitric oxide synthesis in patients with coronary artery disease and stable angina.

AIMS: Inhibition of nitric oxide synthesis causes a decrease in the basal diameter of normal distal epicardial coronary arteries in normal subjects. The effects of inhibition of nitric oxide in atheromatous coronary arteries is unknown. This study assessed the effects of the inhibition of nitric oxide synthesis in epicardial coronary arteries in patients with coronary artery disease. METHODS AND RESULTS: The effects of an intracoronary infusion of NG-monomethyl-L-arginine (LNMMA, an inhibitor of nitric oxide synthesis), were studied in 13 patients with chronic stable angina and coronary artery disease. The diameter of angiographically normal proximal and distal segments and coronary stenoses was measured by quantitative angiography. In response to an LNMMA infusion of 16 mumol min-1 for 4 min there was a significant reduction (P < 0.01) in the luminal diameter of the distal segments of diseased arteries (from 1.32 +/- 0.07 to 1.17 +/- 0.06 mm) and at the site of stenosis (from 1.15 +/- 0.22 to 1.06 +/- 0.20 mm), but no change (P = NS) in the luminal diameter of the proximal segments (from 3.16 +/- 0.12 to 3.08 +/- 0.14 mm) of diseased arteries. CONCLUSIONS: The average effect of inhibition of basal nitric oxide synthesis in epicardial coronary arteries in patients with stable angina and coronary artery disease was only distal constriction. Coronary stenoses constricted at the highest LNMMA concentration.

Angiographic characteristics of infarct-related and non-infarct-related stenoses in patients in whom stable angina progressed to acute myocardial infarction.

BACKGROUND: In patients with coronary artery disease, angiographic and postmortem studies have shown that coronary stenoses in infarct-related arteries often have complex morphology. It is not known whether in patients with multivessel disease stenosis morphology in non-infarct-related arteries is different from those of the infarct-related arteries. METHODS AND RESULTS: In 24 consecutive patients we examined the angiographic characteristics of both the infarct-related stenoses and non-infarct-related stenoses before and after spontaneous acute myocardial infarction, by visual inspection and computerized edge detection of coronary angiograms. Before myocardial infarction, the severity of the infarct-related stenoses was <50% in 14 patients and > or =50% in 10 patients (p=not significant) and of non-infarct-related stenoses was <50% in 16 and > or=50% in 13. A significantly greater proportion of infarct-related stenoses with severity > or =50% progressed to non-Q-wave than to Q-wave myocardial infarction (71% vs 50%, p < 0.05). Before myocardial infarction, the percentage of concentric, eccentric, and irregular infarct-related stenoses was 8%, 13%, and 50%, respectively, whereas in the non-infarct-related stenoses it was 62%, 17%, and 21%, respectively (p < 0.01). A similar proportion of irregular morphology progressed to Q-wave or non-Q-wave myocardial infarction. CONCLUSIONS: In patients with stable angina who had acute myocardial infarction develop, the infarct-related and non-infarct-related stenoses on average are similar in severity but different in morphology. Nonsevere stenoses more frequently progress to Q-wave than to non-Q-wave myocardial infarction.

Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans.

BACKGROUND: NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis, was used to determine the effects of inhibition of nitric oxide synthesis in the human coronary circulation. METHODS AND RESULTS: Twelve patients (mean age, 52 +/- 2 years) with normal epicardial coronary arteries were studied. The surface ECG, systemic blood pressure, and coronary venous oxygen saturation (coronary SvO2), an index of coronary blood flow, were monitored continuously. Coronary artery diameter was measured by quantitative arteriography. L-NMMA was given as intracoronary infusions at 2 mL/min via the diagnostic arteriography catheter. In two patients, low doses (0.01 to 5 mumol/min) of L-NMMA were infused into the nondominant right coronary artery. There was no evidence of ischemia in these patients, who were not included in the final analysis. In 10 patients, higher doses of L-NMMA (4, 10, and 25 mumol/min, each for 5 minutes) were infused into the left coronary artery. In six patients, incremental doses of acetylcholine were infused (1, 10, and 100 nmol/min, each for 3 minutes) before and after the L-NMMA infusion. Finally, in all patients, sodium nitroprusside, a nitric oxide donor, was infused. No patient developed myocardial ischemia. The heart rate and systemic blood pressure remained unchanged throughout the infusions. L-NMMA (25 mumol/min), compared with the control saline infusion, caused a significant reduction in distal (-5.9 +/- 2.1%, P = 0.021) but not proximal left anterior descending coronary artery (LAD) diameter and a fall in coronary SvO2 from 37.5 +/- 2.8% to 34.3 +/- 2.8% (P = 0.019). Sodium nitroprusside dilated the proximal (17.8 +/- 6.9%, P = 0.033) and distal (24.5 +/- 6.5%, P = 0.006) LAD and increased the coronary SvO2 to 61.6 +/- 5.0% (P = 0.0002). Acetylcholine caused significant dilatation of the distal (13.8 +/- 5.4%, P = 0.049) but not proximal LAD and a significant increase in coronary SvO2 from 36.5 +/- 3.5% to 59.2 +/- 2.8% (P < 0.0001). After L-NMMA, acetylcholine-induced dilatation of the distal LAD was abolished, but the rise in coronary SvO2 was unchanged. CONCLUSIONS: Inhibition of nitric oxide synthesis in the human coronary circulation caused a decrease in basal distal LAD diameter and basal coronary blood flow assessed by coronary SvO2, indicating that there is a small basal release of nitric oxide in the distal epicardial coronary arteries and resistive vessels. Distal epicardial coronary artery dilatation in response to acetylcholine is nitric oxide dependent, but coronary resistive vessel dilatation is not.

Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction.

BACKGROUND: The ability of the coronary vascular bed to dilate and thus increase blood flow to the myocardium may be impaired in coronary artery disease, even in regions of myocardium supplied by an angiographically normal coronary artery. If this kind of vasomotor dysfunction was present or accentuated after acute myocardial infarction, it might influence the extent of ischemia and necrosis in areas not directly injured by the infarction. METHODS: We studied 13 patients (mean [+/- SD] age, 62 +/- 11 years) with single-vessel coronary artery disease after they had received thrombolytic therapy for myocardial infarction. Using positron-emission tomography (PET) with oxygen-15-labeled water, we measured regional myocardial blood flow under basal conditions and after the intravenous administration of dipyridamole (0.5 mg per kg of body weight over a period of four minutes) 8 +/- 3 days after infarction in all 13 patients (1-week study) and 6 +/- 2 months after infarction in 9 of the 13 (6-month study). On both occasions we measured blood flow both in the infarcted region and in a region of myocardium that was remote from the infarcted region and supplied by a normal artery. RESULTS: At the one-week PET study, the coronary vasodilator response (the ratio of the myocardial blood flow after the administration of dipyridamole to basal blood flow) was 1.12 +/- 0.50 in the infarct-related artery and 1.53 +/- 0.36 in the remote region (P = 0.015). At the six-month study, the coronary vasodilator response was 1.42 +/- 0.37 in the infarcted region and 2.19 +/- 0.69 in the remote region (P = 0.004 for the comparison with the infarcted region; P = 0.011 for the comparison with the remote region at the one-week study). The value in remote myocardium remained lower than that in similar regions in 10 control patients, who had single-vessel coronary artery disease but no evidence of myocardial infarction (3.17 +/- 0.72; P = 0.009). CONCLUSIONS: After acute myocardial infarction, there is a severe vasodilator abnormality involving not only resistance vessels in infarcted myocardium, but also those in myocardium perfused by normal coronary vessels. This dysfunction may affect the extent of myocardial ischemia and necrosis after coronary occlusion.

Rapid access arrhythmia clinic for the diagnosis and management of new arrhythmias presenting in the community: a prospective, descriptive study.

OBJECTIVE: To investigate whether a rapid access approach is useful for the evaluation of patients with symptoms suggestive of a new cardiac arrhythmia. DESIGN: Prospective, descriptive study. SETTING: Secondary care based rapid access arrhythmia clinic in West London, UK. PARTICIPANTS: Patients referred by their general practitioner or the emergency department with symptoms suggestive of a new cardiac arrhythmia. MAIN OUTCOME MEASURES: Number of patients with a newly diagnosed significant arrhythmia. Number of patients with diagnosed atrial fibrillation. Number of eligible, moderate, and high risk patients treated with warfarin. RESULTS: Over a 25 month period 984 referrals were assessed. The mean age was 55 years (range 20-90 years) and 56% were women. The median time from referral to assessment was one day. A significant cardiac arrhythmia was newly diagnosed in 40% of patients referred to the RAAC. The most common arrhythmia was atrial fibrillation, with 203 new cases (21%). Of these, 74% of eligible patients over 65 were treated with warfarin. Other arrhythmias diagnosed were supraventricular tachycardias (127 (13%)), conduction disorders (43 (4%)), and non-sustained ventricular tachycardia (21 (2%)). Vasovagal syncope was diagnosed for 53 patients (5%). The most frequent diagnosis was symptomatic ventricular and supraventricular extrasystoles (355 (36%)). CONCLUSION: A rapid access arrhythmia clinic is an innovative approach to the diagnosis and management of new cardiac arrhythmias in the community. It provides a rapid diagnosis, stratifies risk, and leads to prompt initiation of effective treatment for this population.

Myocardial beta adrenoceptor density in primary and secondary left ventricular hypertrophy.

OBJECTIVES: Myocardial beta-adrenoceptor density has been found to be reduced in hypertrophic cardiomyopathy, even when systolic function is preserved. Our purpose in the current study was to investigate whether beta-adrenoceptor down-regulation was unique to hypertrophic cardiomyopathy, or is also present in secondary myocardial hypertrophy. METHODS: Myocardial beta-adrenoceptor density was measured in 11 patients with hypertrophic cardiomyopathy, eight patients with left ventricular hypertrophy secondary to arterial hypertension or aortic valve disease and 18 normal control subjects, using positron emission tomography with 11C-CGP-12177 as the myocardial beta-adrenoceptor ligand. RESULTS: Reflecting the natural incidence of the conditions, the age of the hypertrophic cardiomyopathy patients was 37 (10) [mean (SD), range 20-51] years and that of the secondary hypertrophy patients 64 (18), [range 26-80] years; P < 0.01. The controls' ages were 50 (13), [range 21-65] years; however, since beta-adrenoceptor density is known to be influenced by age, the controls' data was split into groups matched to the hypertrophic cardiomyopathy and secondary hypertrophy patient sets. For the hypertrophic cardiomyopathy patients, mean left ventricular beta-adrenoceptor was 7.70 (1.86) pmol.g-1 compared to 10.17 (2.44) pmol.g-1 for a matched set of 15 controls; P < 0.01. In secondary left ventricular hypertrophy, beta-adrenoceptor was 6.35 (1.70) pmol.g-1 compared to 9.16 (2.00) pmol.g-1 for a matched set of 10 controls; P < 0.01. Plasma noradrenaline was 5.5 (2.2) nmol.l-1 in hypertrophic cardiomyopathy and 2.5 (1.0) nmol.l-1 for the matched controls; P < 0.01. The results for adrenaline were 2.2 (1.1) vs 0.4 (0.3) nmol.l-1 respectively; P < 0.001. For the secondary hypertrophy patients, the corresponding figures were 2.5 (1.2) vs 2.5 (1.0) nmol.l-1 for noradrenaline for patients and controls respectively (P = ns); and for adrenaline 0.2 (0.1) and 0.3 (0.2) nmol.l-1 respectively, P = ns. On multiple regression analysis, no relationships could be demonstrated amongst plasma catecholamines, beta-adrenoceptor, myocardial blood flow and echocardiographic E/A ratio and fractional shortening. CONCLUSION: Myocardial beta-adrenoceptor density appears to be comparably decreased in both primary and secondary left ventricular hypertrophy in the presence of preserved left ventricular systolic function.