Endothelium-dependent and -independent perfusion reserve and the effect of L-arginine on myocardial perfusion in patients with syndrome X.

BACKGROUND: Impaired vasodilatation capacity in patients with angina pectoris and a normal coronary arteriogram (syndrome X [SX]) has been reported. Most studies report on the response in epicardial vessels. This does not necessarily reflect compromised myocardial microcirculation. Lack of the NO precursor L-arginine has been suggested as a possible cause. METHODS AND RESULTS: Myocardial blood flow (MBF) was measured, using PET, at rest (MBF-rest) and during intravenous dipyridamole (MBF-DIP) in 25 women (mean age 53+/-7 years) with SX. Thirty healthy volunteers served as controls. One group (A) consisted of 15 age-matched female volunteers (54+/-10 years). The other control group consisted of 15 young healthy women (B; 24+/-5 years). In 12 SX patients, MBF-rest and MBF during cold pressor testing were also measured after infusion of L-arginine (6.7 g/min for 45 minutes). The increase in MBF after cold pressor testing was similar in the SX group compared with controls. L-arginine did not affect MBF-rest (0.83+/-0.14 versus 0.89+/-0.13 mL. g-1. min-1) or MBF after cold pressor test (0.95+/-0.10 versus 1. 03+/-0.17 mL. g-1min-1). In contrast, the hyperemic response to DIP was blunted compared with the group A controls (1.68+/-0.49 versus 2. 34+/-0.45 mL. g-1. min-1, P<0.05); this resulted in a significant reduction of the coronary flow reserve in SX patients relative to controls (2.03+/-0.53 versus 2.96+/-0.63 mL. g-1. min-1, P<0.01). CONCLUSIONS: In patients with SX, the microcirculatory response to cold, reflecting the endothelium function, is normal and unaltered by intravenous L-arginine. This suggests preserved microcirculatory endothelial function. However, a markedly attenuated hyperemic flow and flow reserve after DIP suggest a dysfunction of the adenosine-mediated endothelium-independent vasodilatation at the microcirculatory level in these patients.

Enhanced exercise-induced hyperkalemia in patients with syndrome X.

OBJECTIVES: The purpose of this study was to determine whether patients with syndrome X have altered potassium metabolism. BACKGROUND: Patients with syndrome X have angina pectoris and exercise induced ST segment depression on the electrocardiogram despite normal coronary angiograms. Increasing evidence suggests that myocardial ischemia is uncommon in these patients. Altered potassium metabolism causing interstitial potassium accumulation in the myocardium may be an alternative mechanism for chest pain and ST segment depression in syndrome X. METHODS: We compared the magnitude of exercise-induced hyperkalemia in 16 patients with syndrome X (12 female and four male, mean +/- SD age 53 +/- 6 years) and 15 matched healthy control subjects. The participants underwent a bicycle test at a fixed load of 75 W for 10 min, and blood samples were taken for analysis of potassium, catecholamines and lactate before, during and in the recovery period after exercise. In five patients with syndrome X, the test was repeated during alpha1 adrenoceptor blockade. RESULTS: Baseline concentrations of serum potassium, plasma catecholamines and plasma lactate were similar in patients and control subjects. The rate of exercise-induced increment of serum potassium was increased in the patients (70 +/- 29 vs. 30 +/- 21 micromol/liter/min in control subjects, p < 0.001). Six patients, who stopped before 10 min of exercise, showed very rapid increments in serum potassium concentration. Compared to the control subjects, patients also demonstrated larger increments in rate-pressure product, plasma norepinephrine and lactate concentrations during exercise. The rate of serum potassium increment correlated with the rate of plasma norepinephrine increment in the patients (r = 0.63, p < 0.02), but not in the control subjects (r = 0.01, p = 0.97). Blockade of alpha1 adrenoceptors decreased systolic blood pressure at baseline, but did not influence the increment of serum potassium, plasma catecholamines and lactate. CONCLUSIONS: Patients with syndrome X have enhanced exercise induced hyperkalemia in parallel with augmented increases of circulating norepinephrine and lactate. The prevailing mechanisms behind the abnormal potassium handling comprise sources distinct from alpha1-adrenoceptor activation.

Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms.

OBJECTIVES: The purpose of this study was to investigate the relationship between arterial and coronary sinus endothelin (ET) concentrations and coronary vasomotor responses during rapid atrial pacing in patients with chest pain and normal coronary arteriograms (CPNA). BACKGROUND: Plasma ET concentrations are significantly higher in CPNA patients than in healthy control subjects. METHODS: We investigated 19 carefully characterized CPNA patients (14 women; mean age 53 +/- 9 years) of whom 10 had positive electrocardiographic responses to exercise. The percentage fall in coronary vascular resistance (%d.CVR) after 10 min of rapid atrial pacing was determined using a thermodilution pacing catheter. Plasma ET concentrations were measured by radioimmunoassay on simultaneously drawn arterial and coronary sinus samples. RESULTS: No significant differences in ET concentrations were observed between men and women, but a strong statistical trend suggested that %d.CVR was lower in women than men (27[23 to 31]% vs. 34[29 to 45]%--median[interquartile range]; p = 0.07). Simple regression analysis including only the women (n = 14) suggested a significant relationship between baseline arterial ET concentrations and %d.CVR (R2 = 0.34; p = 0.06). Furthermore, stepwise multivariate regression analysis of the group as a whole indicated that both gender (p = 0.03) and baseline arterial ET concentration (p = 0.02) were independently predictive of %d.CVR (R2 = 0.44; overall p = 0.02); this relationship predicts that women with high ET levels would have the lowest %d.CVR during pacing. CONCLUSIONS: These data support the hypothesis that elevated ET activity may be associated with reduced coronary flow responses during rapid atrial pacing in CPNA patients.

Frequency of systemic microvascular dysfunction in syndrome X and in variant angina.

In addition to coronary vascular abnormalities, patients with syndrome X and variant angina often have systemic vascular symptoms. To determine whether these patients exhibit a generalized abnormality of vasoreactivity, we used high-resolution ultrasound to compare flow responses and endothelial function in the brachial artery in 21 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls. Arterial diameter was measured at rest, after reactive hyperemia (endothelium-dependent flow-mediated vasodilation), and after sublingual glyceryl trinitrate (endothelium-independent vasodilation). The magnitude of hyperemic flow response was measured after transient forearm occlusion. Flow-mediated dilation in the brachial artery did not differ among patients with syndrome X, variant angina, and controls (2.7 +/- 2.3%, 3.8 +/- 3.5%, and 4.2 +/- 3.0%). Endothelium-independent vasodilation in the brachial artery was similar in the 3 groups (16.0 +/- 7.2%, 12.7 +/- 4.6%, and 14.8 +/- 4.9%). Despite a considerable overlap, reactive hyperemia was lower in patients with syndrome X than in patients with variant angina and controls (342+/-86% vs 466+/-184% and 452+/-104%; p < 0.05). These findings indicate that a substantial proportion of patients with syndrome X have a systemic microvascular abnormality, whereas variant angina is predominantly a segmental disorder of conduit vessels.

Effects of doxazosin on exercise-induced angina pectoris, ST-segment depression, and insulin sensitivity in patients with syndrome X.

A significant proportion of patients with cardiac syndrome X have impaired coronary vasodilator capacity, which is thought to be caused by an increased sympathetic drive. The alpha1-adrenoceptor blocker, doxazosin, increases the coronary vasodilator reserve in patients with syndrome X. To study whether the augmentation is associated with clinical improvement in patients, we conducted a double-blind, placebo controlled, crossover study with doxazosin 1 to 4 mg once daily for 10 weeks in 16 patients with syndrome X (14 women and 2 men; mean +/- SD age 56+/-5 years). Time to angina, exercise duration, time to 0.1 mV ST-segment depression, and maximal ST-segment depression during bicycle exercise testing were compared after treatment with doxazosin 2 mg or placebo for 5 weeks and again after treatment with doxazosin 4 mg or placebo for 10 weeks. Insulin sensitivity was assessed by the minimal model after 10 weeks of doxazosin or placebo treatment. Twelve patients completed the protocol. Doxazosin 4 mg/day decreased systolic blood pressure at rest (109+/-16 vs 125+/-18 mm Hg, p <0.05) and increased basal heart rate (85+/-9 vs 76+/-11 beats/min, p <0.05), whereas hemodynamics were unaffected during exercise. Time to angina, exercise duration, time to 0.1 mV ST-segment depression, and maximal ST-segment depression were similar during treatment with doxazosin and placebo irrespective of the doxazosin dose. Insulin sensitivity was not different with doxazosin and placebo. In conclusion, alpha1 blockade does not significantly improve exercise duration, angina pectoris, and ST-segment depression despite a favorable vasodilator effect in patients with syndrome X. The absent clinical efficacy of doxazosin may challenge the use of the coronary vasodilator capacity as an appropriate method to subclassify patients with syndrome X.

Impact of impaired coronary flow reserve and insulin resistance on myocardial energy metabolism in patients with syndrome X.

To evaluate the role of a decreased coronary flow reserve in the genesis of angina pectoris in patients with syndrome X, we studied myocardial hemodynamics and metabolism at rest, during pace stress, and in the recovery period after pacing in 18 consecutive patients with syndrome X and in 10 control subjects. By means of positron emission tomography or the intracoronary flow-wire method, patients were subclassified as having microvascular angina (MA, n = 8) when coronary flow reserve was reduced (<2.5) or no microvascular angina (non-MA, n = 10) when coronary flow reserve was preserved (> or =2.5). At rest, coronary sinus blood flow was increased in MA patients. During pace stress, coronary sinus blood flow increased by 39 +/- 6% in MA patients versus 67 +/- 12% in non-MA patients and 69 +/- 7% in controls (p <0.05). Patients with non-MA revealed fasting hyperinsulinemia, increased arterial concentration of free fatty acids, and a similar tendency for beta-hydroxybutyrate. Oxygen extraction and carbon dioxide release did not differ between groups. Net myocardial lactate release was not observed in any patient during pace stress and myocardial energy metabolism was preserved in all patients with syndrome X. During pacing, myocardial uptake of free fatty acids and beta-hydroxybutyrate was increased in non-MA patients. Myocardial uptake of free fatty acids correlated positively and myocardial glucose and lactate uptake correlated inversely with arterial concentrations of free fatty acids in all subjects. Metabolic evidence of myocardial ischemia is uncommon in patients with syndrome X, irrespective of a globally reduced coronary flow reserve. Although patients with syndrome X can be subclassified according to presence of a microvascular or a metabolic disorder, angina pectoris and ST-segment depressions coexist with a preserved global myocardial energy efficiency in all patients.

Use of collagen shields in cataract surgery.

A randomized, prospective, multicenter study evaluated the efficacy and safety of using collagen shields to deliver drugs after cataract surgery. Collagen shields saturated with an antibiotic and a steroid were placed in 90 eyes postoperatively. A control group of 93 eyes received the same drugs through a peribulbar/retrobulbar injection. One day after surgery, the shield group had significantly less corneal edema, conjunctival hemorrhaging, and postoperative pain and fewer corneal opacities. All symptoms except the conjunctival hemorrhaging disappeared by day seven. Our study suggests that using collagen shields for drug delivery after cataract surgery decreases tissue damage and increases patient comfort without adverse side effects.

[Radioiodine therapy of thyrotoxicosis in a central hospital]. / Radiojodterapi af tyreotoksikose på et centralsygehus.

The aim of this study was to assess the results of 131-I therapy on hyperthyroidism. 131-I doses were individually calculated on the basis of thyroid gland classification, size and iodine-uptake. All patients were pretreated with propylthiouracil or methimazole. Seventy-nine patients treated with radio-iodine during the period 1.3.81-1.6.88 were followed up. The period of observation was 12-100 months (median 57). After eight years and four months the cumulative incidence of hypothyroidism was 45%, being 69% for diffuse goitre, 31% for multinodular goitre and 24% for solitary adenoma. A Cox-analysis showed a significantly greater cumulative incidence of hypothyroidism in patients with diffuse goitre as opposed to non-diffuse. From our data we conclude that radio-iodine therapy of hyperthyroidism with individually calculated doses of 131-I is a satisfactory method, assuming that patients are subjected to lifelong follow-up.

[Stent implantation in genuine coronary vessels--with and without guidance of intracoronary ultrasound]. / Stentimplantation i genuine koronarkar--med og uden vejledning af intrakoronar ultralyd.

The purpose of the present study was to evaluate the clinical and angiographic results of implantation of stents in the native coronary circulation. In group A (n: 33) implantation was assessed by angiography, in group B (n: 17) also by ICUS. There were no procedure related deaths, transmural myocardial infarctions or acute coronary by-pass operations (CABG). The diameter of stenosis before treatment was 86% and 82% in group A and B, respectively. In both groups an overdilatation was seen following stent implantation, 5% in group A versus 22% in group B (p < 0.01). At four months follow-up 80% in group A and 81% in group B were symptom-free or improved (NS). Angiographic restenosis (> or = 50% reduction of vessel diameter) was found in 10.3% in group A versus 20.0% in group B (NS). Our results are in accordance with other coronary stent studies showing reduced acute coronary occlusion and CABG incidence and a low restenosis rate as compared to conventional balloon angioplasty. The role of ICUS in the implantation of intracoronary stents remains unsettled.

[Left ventricular hypertrophy in patients with aortic stenosis. A comparison between electrocardiography and echocardiography]. / Venstre ventrikel-hypertrofi hos patienter med aortastenose. En sammenligning mellem elektrokardiografi og ekkokardiografi.

Using echocardiography (ECHO) as the reference method, the aim of this study was to determine the sensitivity, specificity, and predictive value of the electrocardiogram (ECG) in detection of left ventricular hypertrophy (LVH) in patients with aortic stenosis. Forty-one patients, 18 men and 23 women aged 25-80 years (mean 49 years) with uncomplicated aortic stenosis were studied. ECG-LVH was estimated by standard fixed voltage criteria. ECHO-LVH was defined according to left ventricular mass (LV mass) calculated by the Penn method. In the total material, the correlation between ECG-LVH and ECHO-mass was poor (r = 0.56, p < 0.05). The sensitivity and specificity of the ECG was respectively 50% and 100%. The positive predictive value of the ECG in detection of LVH was high (100%). We conclude that the sensitivity of the ECG in detection of LV hypertrophy is unsatisfactorily low. Accordingly, it is recommended that echocardiography be performed in all patients suspected of aortic stenosis.

[Intracoronary ultrasonography--a supplement to coronary arteriography]. / Intrakoronar ultralydundersøgelse--et supplement til koronararteriografi.

Intracoronary ultrasound is a new technique, by means of which it is possible for the first time to visualise coronary artery wall structures in vivo. Compared to conventional coronary angiography the advances of this new modality appear to be: 1) Improved diagnosis of minimal and non-obstructive atherosclerosis; 2) Characterisation of plaque morphology, thereby being an aid in decision on interventional procedures (PTCA, atherectomy, stent placement); 3) Better delineation of coronary artery lumen area, which improves the accuracy of stenosis graduation both before and after interventional procedures. The examination can be performed in up to 95% of cases. The procedure appears to be safe with a reported complication rate of myocardial infarction and bypass surgery of 0.16% in 1837 cases; transient coronary artery spasms occurred in about 3%. Complications are predominantly associated with interventional procedures. Although intracoronary ultrasound has mainly been used for research purposes, results of ongoing trials assessing its clinical utility, as well as technological improvement providing more consistent image quality, suggest that the procedure will evolve into an important adjunct to coronary angiography.

Left ventricular opacification after intravenous injection of Albunex. The effect of different administration procedures.

A clinical study has been performed to investigate the influence of different administration procedures on the degree of contrast enhancement of the left ventricle. The administration variables assessed included Albunex injection rate, arm position, flushing rate and flushing fluid. Twenty-four healthy male volunteers were included. Compared to an injection rate of 1 ml/sec an injection rate of Albunex of 2 ml/sec caused an earlier appearance of contrast in the right ventricle (1 heart beat), whereas transpulmonary passage was not influenced. Horizontal arm position caused a delay in time to peak intensity of 2 to 3 heart beats in both systole and diastole as compared to elevated arm position. Injection rate of 1 ml/sec compared to 2 ml/sec caused a higher peak intensity and mean area under the curve and a longer mean time to peak intensity and transit time. Differences varied from 6 to 230 grey level units out of mean values of 2500. All the observed differences were small and thus probably of no clinical importance. The present study indicates that improvements in the pressure stability characteristics of the albumin microspheres in Albunex have been achieved. This implies that a simple administration procedure can be used. It is recommended that the contrast agent, after resuspension, is injected through a three-way stop cock cannula, followed by 10 ml of saline for flushing. The cannulas or syringes used should be no smaller than 20 G. The injection rate should be 1-2 ml/sec, depending on the diameter of the cannula. By using this procedure, a reliable transpulmonary passage and left ventricular opacification may be obtained.