Zenon S. Kyriakides

Coronary collateral circulation in coronary artery disease and systemic hypertension

The extent and functional capacity of coronary collateral circulation in patients with systemic hypertension has not been elucidated. In the present study, 313 patients with coronary artery disease were studied to evaluate coronary collateral circulation in relation to the presence of systemic hypertension and left ventricular hypertrophy. Patients had greater than or equal to 95% diameter luminal obstruction of either the left anterior descending or the right coronary artery. Patients were classified into 2 groups: The hypertensive group consisted of 61 patients, mean age 55 +/- 9 years, with systemic hypertension, and the normotensive group consisted of 252 patients, mean age 53 +/- 8 years, without hypertension. The hypertensive group had more severe angina pectoris and less history of healed myocardial infarction than the normotensive group (p less than 0.001). Left ventricular wall thickness was 1.26 +/- 0.1 cm in the hypertensive and 1.03 +/- 0.06 cm in the normotensive group (p less than 0.001). The hypertensive group had more extensive coronary collateral circulation than the normotensive group (p less than 0.01). There was a positive relation between coronary collateral circulation and left ventricular wall thickness (p less than 0.001). These results indicate that patients with systemic hypertension and coronary artery disease have an increase in coronary collateral circulation corresponding to the degree of left ventricular wall thickness.

The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease

OBJECTIVES This study sought to compare hormone replacement therapy (HRT), simvastatin and their combination in the management of hypercholesterolemia in postmenopausal women with coronary artery disease (CAD). BACKGROUND Lipid-lowering therapy reduces mortality in hypercholesterolemic women with CAD. In postmenopausal women HRT seems to increase survival, particularly those with ischemic heart disease, and this is partly due to changes in lipid levels. METHODS We studied 16 postmenopausal women with CAD and fasting total cholesterol <200 mg/dl and low-density lipoprotein (LDL) cholesterol <130 mg/dl. We compared HRT (0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone acetate daily) with simvastatin (20 mg daily) and their combination in a randomized, crossover, placebo-controlled study. Each treatment period was 8 weeks long with a 4-week washout interval between treatments. RESULTS Simvastatin, HRT and their combination significantly reduced total and LDL cholesterol by 35%, 13%, and 33% and 45%, 20%, and 46%, respectively, compared to placebo (p < 0.001). However, simvastatin and the combination was superior to HRT (p < 0.001), and none of our patients had total cholesterol <180 mg/dl and LDL cholesterol <100 mg/dl on HRT alone. High-density lipoprotein cholesterol was not significantly affected by any of the active treatments, and triglycerides were lower during simvastatin therapy compared to placebo (p < 0.01). Apolipoprotein B was significantly reduced by simvastatin, alone and combined with HRT, by 39% and 35%, respectively, compared to placebo (p < 0.001). Alone and in combination with simvastatin, HRT significantly increased apolipoprotein A-I by 11% and 12%, respectively, compared to placebo (p < 0.05) and decreased lipoprotein (a) by 23% and 33%, respectively, compared to placebo (p < 0.05), whereas simvastatin had no significant effect on either of these parameters. CONCLUSIONS In hypercholesterolemic postmenopausal women with CAD, HRT exerts beneficial effects on plasma lipids but the levels currently recommended for secondary prevention are not achieved. Hormone replacement therapy combined with simvastatin is well tolerated and extremely effective, as the two therapies seem to be additive.

Does passive leg raising increase cardiac performance? A study using Doppler echocardiography

Passive leg raising is commonly used for the initial treatment of hypovolemic shock. However, there are many reports which have pointed out that it does not produce significant autotransfusion effect. We tried to evaluate the effects of passive leg raising on the cardiovascular performance in coronary artery disease patients in stable condition. We studied 31 patients of 51 +/- 10 years. Two M-mode echocardiographic and continuous wave Doppler studies of aortic flow were obtained. The first was performed while the patient was lying on the left side and the second after passive leg elevation. Left ventricular end-diastolic dimension increased by 0.40 +/- 0.82 cm (P = 0.007), fractional shortening by 2.5 +/- 6% (P = 0.01), peak aortic blood velocity by 5 +/- 14 cm/s (P = 0.02), and velocity time integral by 1.7 +/- 3.0 cm (P = 0.0007). From the above it is concluded that passive leg elevation really does increase preload, and consequently cardiac performance, by the classical Frank-Staring relationship in normovolemic coronary artery disease patients.

The effects of raloxifene and simvastatin on plasma lipids and endothelium

AbstractPurpose: Raloxifene is a selective estrogen receptor modulator and an attractive alternative to estrogen replacement as it obviates the need for a progestin and does not increase C-reactive protein levels. We compared the effects of simvastatin and raloxifene treatments on the lipid profile, the levels of adhesion molecules and the endothelium dependent and independent vasoreactivity. Subjects & Methods: We treated 12 postmenopausal women with hypercholesterolemia and coronary artery disease with raloxifene 60 mg/day and simvastatin 20 mg/day in a randomized, double-blind, crossover study. Each treatment period was 8 weeks long with a 4-week washout interval. Plasma lipids and cellular adhesion molecules were evaluated and peripheral blood flow studies with venous occlusion plethysmography were performed. Results: Both simvastatin and raloxifene significantly reduced total [33% (27–40), 12% (0–24)] and LDL [44% (36–52), 16% (0–33)] cholesterol compared to baseline values (p < 0.05) but simvastatin was more effective than raloxifene (p < 0.005). None of the treatments had any significant effect on HDL cholesterol and triglyceride levels. Only raloxifene significantly reduced Lp(a) [18% (1–36)] and ICAM-1 [17% (8–25)] and VCAM-1 [24% (15–33)] plasma levels compared to baseline (p = 0.019, p < 0.0001 and p = 0.003, respectively). Hyperemic blood flow response on raloxifene was significantly higher compared to baseline [52% (0–105)], (p < 0.05), whereas no significant change was noted on simvastatin. Endothelium independent blood flow induced by nitroglycerine was not influenced by either active treatment. Conclusions: Raloxifene administration is associated with lower ICAM-1, VCAM-1 and Lp(a) plasma levels and enhanced endothelium dependent dilation compared to simvastatin although simvastatin is more powerful in total and LDL cholesterol reduction.

Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia

OBJECTIVE Promoting angiogenesis may be an effective treatment for patients with diffuse peripheral vascular disease. This study investigated whether estrogen can promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia. METHODS AND RESULTS Ischemia was induced in one hindlimb of 24 oophorectomized New Zealand White rabbits. Ten days later (day 0), they were randomized into 4 groups for intramuscular treatment in the ischemic limb: controls receiving saline at day 0; Estrogen-1 group receiving estradiol valerate, modified release (EVMR), 1 mg/kg at day 0; Estrogen-2 group receiving EVMR 1 mg/kg at days 0 and 15; and Estrogen-3 group receiving EVMR 2 mg/kg at day 0. Revascularization was evaluated by clinical indexes, such as ischemic/normal limb systolic blood pressure (BPR), and capillary density/muscle fiber in the abductor muscle of the ischemic limb at the time of death (day 30). At day 30 the BPR was increased in all groups (0.39+/-0.08 in the controls, 0.52+/-0.11 in the Estrogen-1 group, 0.65+/-0.13 in the Estrogen-2 group and 0.61+/-0.16 in the Estrogen-3 group, F=2.39, P=0.04). The capillary/muscle fiber at day 30 was 0.87+/-0.09, 1.08+/-0.15, 1.01+/-0.14 and 1.10+/-0.9 (F=5.01, P=0.01), respectively, in the 4 groups. The capillary/muscle fiber was related to BPR (r=0.48, P<0.02) and to 17-beta estradiol plasma levels of day 15 (r=0.58, P=0.003) and of day 30 (r=0.46, P<0.02). CONCLUSION Administration of estrogen promotes angiogenesis and perfusion in ischemic rabbit hindlimbs. Thus, estrogen may represent a new therapeutic modality in the management of arterial insufficiency.

Effects of atrial, ventricular, and atrioventricular sequential pacing on coronary flow reserve.

KOLETTIS, T.M., et al.: Effects of Atrial, Ventricular, and Atrioventricular Sequential Pacing on Coronary Flow Reserve. Experimental animal data have indicated that altered left ventricular depolarization sequence as a result of right ventricular pacing may diminish coronary blood flow in the distribution of the left anterior descending coronary artery. To further investigate this, we compared the effects of atrial, ventricular, and atrioventricular (AV) sequential pacing on coronary flow reserve. Twenty‐seven patients (24 male, mean age 55 ± 7 years) with normal left anterior descending coronary arteries were studied. Coronary flow reserve was calculated as the ratio of mean flow velocity at maximal coronary vasodilatation to mean flow velocity at baseline. The study consisted of two parts. In the first part, AV sequential pacing was compared to atrial pacing at the same rate; coronary flow reserve did not differ significantly between the two pacing modes (14 patients, 4.85 ± 1.88 vs 5.47 ± 1.55, respectively, P > 0.05). In the second part, all three pacing modalities were compared; coronary flow reserve was significantly higher during ventricular compared to AV sequential pacing, but not significantly different compared to atrial pacing (3.69 ± 1.42 vs 2.90 ± 0.86 vs 3.11 ± 0.89, respectively, P < 0.05). This difference was secondary to a significant decrease in mean baseline velocity during ventricular pacing, while mean velocity during hyperemia was comparable between the three pacing modes. It is concluded that AV sequential pacing does not appear to exert a significant effect on coronary flow reserve. Ventricular pacing, however, may lower resting coronary blood velocity in some patients, without affecting maximal coronary blood velocity, resulting in a higher coronary flow reserve.

Acute Endothelin-A Receptor Antagonism Prevents Normal Reduction of Myocardial Ischemia on Repeated Balloon Inflations During Angioplasty

BackgroundMyocardial ischemia and reperfusion are associated with increased production of endothelin (ET)-1. Methods and ResultsWe examined the effects of BQ-123, a selective ETA receptor antagonist, in 80 patients. All patients were randomly allocated to an intracoronary infusion of saline or BQ-123 (6 &mgr;mol/L over 20 minutes). The reference group consisted of 20 patients undergoing coronary angiography. BQ-123 produced a 10% (P <0.005) increase in distal coronary artery diameter. The main study group consisted of 30 patients undergoing coronary angioplasty. All patients underwent a minimum of 3 balloon inflations (BIs). Surface and intracoronary electrocardiographic ST-segment shift as well as pain score were recorded at the end of each BI. BQ-123 or saline was given by intracoronary infusion between the second and the third BI in random allocation. In the saline group, intracoronary ST-elevation decreased from 1.26±0.55 mV during the first BI to 0.77±0.56 mV during the third BI (P <0.05) and the surface ST elevation decreased from 0.20±0.15 to 0.10±0.07 mV (P <0.05). In the BQ-123 group, the respective values were 1.22±0.48 mV and 1.13±0.62 mV (intracoronary) and 0.17±0.18 and 0.17±0.21 mV (surface) (both P =NS). The decrease in pain score was significantly higher in the saline group (F =5.97, P =0.004). In 30 patients (collateral circulation group), the angioplasty protocol was repeated with the use of a pressure guide wire. BQ-123 produced a significant (F =3.30, P =0.04) decrease in coronary wedge pressure. ConclusionsAcute ETA receptor antagonism prevents the normal reduction of myocardial ischemia on repeated BIs during angioplasty. This may be explained by a “steal” effect through coronary collaterals.

Short-Term Estrogen Reduces Myocardial Infarct Size in Oophororectomized Female Rabbits in a Dose-Dependent Manner

Abstract17β-estradiol, administered acutely, protects ischemic myocardium in male rabbits. In the present study we investigated the effect of short-term estrogen on myocardial infarct size in oophorectomized female rabbits. We oophorectomized 24 sexually mature New Zealand white female rabbits. Twelve animals were left untreated and 12 received oral conjugated estrogens, 0.15 mg/day, for 4 weeks. At a second stage, a third group of 12 oopherectomized female rabbits was treated with intramuscular conjugated estrogens, 1 mg/day, also for 4 weeks. All rabbits underwent 30 minutes of coronary artery occlusion and 2 hours of reperfusion while on anesthesia with IV pentobarbital. Infarct and risk area were delineated by Zn-Cd fluorescent particles and tetrazolium chloride staining. The infarct size was expressed as a percentage of the risk zone (I/R %). Data are reported on 26 animals that survived the treatment period and the experiment. Heart rate, systolic, and mean blood pressure and double product did not differ between the three groups at baseline, ischemia, and reperfusion. The infarct size of the risk zone was significantly smaller in the intramuscular group compared with both the oral and the placebo group (18.5 ± 3.5% vs. 41.3 ± 9.2% and 43 ± 8.4%, respectively, P = 0.03). Conjugated estrogens, administered intramuscularly at a high dose, protect ischemic myocardium in oophorectomized female rabbits.

Painless myocardial ischemia in chronic hemodialysed patients : a real event ?

We investigated the incidence of painless (silent) myocardial ischemia, manifested as S-T segment deviation, by Holter ECG monitoring in patients with chronic renal failure undergoing regular hemodialysis. Forty-five patients underwent Holter ECG monitoring for a continuous 48-hour period covering dialysis and the intermediate period of everyday activity at home. ECG criteria for ischemia were found in 15.5% of patients mainly during and immediately after dialysis with a simultaneous increase of R,S,R + S amplitude. There was no correlation of S-T segment deviation with the existence of cardiac dysfunction and coronary artery disease proved by hemodynamic and angiographic studies. It is concluded that hemodialysis itself seems to play an important role in the genesis of the above ECG findings, possibly by means of serum K and Mg changes.

Absence of Effects of Short-Term Estrogen Replacement Therapy on Resting and Exertional QT and QTc Dispersion in Postmenopausal Women with Coronary Artery Disease

Women, on average, have a longer QT interval on the electrocardiogram and are at higher risk of developing torsade de pointes from antiarrhythmic therapy than men. Although endogenous estrogen may play a role in these sex differences, the effect of estrogen replacement therapy has not been examined. Ten women, 65 ± 7 years of age, wit/i stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease (at least one ≥ 70%) stenosis were studied. All women had been postmenopausal for at least 1 year, and none had ever received hormone replacement therapy (HRT). The patients received standard dose HRT (0.625 mg/day oral conjugated estrogen) or matching placebo for 4 weeks in random order, with crossover after a 4‐week washout period. Exercise testing using the standard Bruce protocol was performed at the end of the first and third months of the study. Antianginal medications remained unchanged throughout the study period. Compared to placebo, HRT caused a significant increase in plasma estradiol levels from 5.55 ± 1.66 to 31.11 ± 14.95 pg/mL (P = 0.001). QT and QTc, as well as QT and QTc dispersion, did not differ at rest and at peak exercise between the two exercise tests. Likewise, other test results, including angina score, exercise time, ST‐T changes, blood pressure, heart rate, and double product were unchanged. Short‐term HRT did not alter cardiac repolarization at rest and during exercise in postmenopausal women with known coronary disease.