Investigating the signal transduction pathways underlying remote ischemic conditioning in the porcine heart.

BACKGROUND: The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine receptor and the PI3K-Akt pathway at the onset of myocardial reperfusion. METHODS AND RESULTS: Domestic pigs (27-35 kg) were subjected to in situ left anterior descending coronary artery ischemia (60 min) followed by reperfusion (180 min) and randomised to the following: (1) Control- No additional intervention; (2) Remote ischemic preconditioning (RIPC)- Four-5 min cycles of lower limb ischemia/reperfusion were administered prior to myocardial ischemia; (3) RIPC + Wort or 8-SPT: Wortmannin (Wort 20 µg/kg, a PI3K inhibitor) or 8-sulfophenyltheophylline (8-SPT 10 mg/kg, an adenosine receptor inhibitor) were administered intravenously 30 s before myocardial reperfusion to RIPC-treated animals; (4) Remote ischemic perconditioning (RIPerC)--Four-5 min cycles of lower limb ischemia/reperfusion were applied 1 min before myocardial reperfusion; (5) RIPerC + Wort or 8-SPT: Wort or 8-SPT were given 30 s before myocardial reperfusion to RIPerC-treated animals. Both RIPC and RIPerC reduced myocardial infarct size (13.3 ± 2.2% with RIPC, 18.2 ± 2.0% with RIPerC versus 48.8 ± 4.2% in control:P < 0.05:N ≥ 5/group). Wortmannin abolished the infarct-limiting effects of RIPC (33.2 ± 6% with RIPC + Wort versus 13.3 ± 2.2% with RIPC:P < 0.05:N ≥ 5/group) but not RIPerC (18.0 ± 3.4% with RIPerC + Wort versus 18.2 ± 2.0% with RIPerC:P > 0.05:N ≥ 5/group). 8-SPT did not influence the infarct-limiting effects of either RIPC or RIPerC. Western blot analysis confirmed Wortmannin-sensitive PI3K and Akt activation at myocardial reperfusion in RIPC-treated hearts. CONCLUSIONS: In the porcine heart, both RIPC and RIPerC both reduce myocardial infarct size and with RIPC but not RIPerC this cardioprotective effect is associated with the activation of the PI3K-Akt pathway at reperfusion.

Epicardial and pericardial adipose tissue: physiological importance and role of imaging techniques.

Epicardial adipose tissue (EAT) is becoming a cardiovascular risk factor. Multiple imaging techniques are used to measure it, each one with its prons and cons. We will review the literature realizing that there is still a lot of work that needs to be done.

Effects of adiponectin in TNF-α, IL-6, and IL-10 cytokine production from coronary artery disease macrophages.

Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.

Remote postconditioning is more potent than classic postconditioning in reducing the infarct size in anesthetized rabbits.

PURPOSE: Postconditioning confers protection to the heart after a potentially lethal episode of prolonged ischemia. There is evidence that it may also be protective when applied at a distal artery. In the present study, we sought to determine whether remote postconditioning within the heart (local) or outside the heart (distal) is effective in salvaging the ischemic heart in vivo and to compare its effect with that of the classic postconditioning. METHODS: Twenty seven open chest New Zealand white anesthetized male rabbits were divided into four groups and were exposed to 30 min regional myocardial ischemia (isc), after ligation of a prominent coronary artery, followed by 3 h reperfusion (rep) after releasing the snare. Control group (n = 7) was subjected to no additional interventions, postC group (n = 6) was subjected to four cycles of 1 min isc/1 min rep of the same coronary artery at the beginning of reperfusion, remote local postC group (n = 7) to four cycles of 1 min isc/1 min rep of another coronary artery 30 s before the end of index isc and remote distal postC group (n = 7) to four cycles of 1 min isc/1 min rep of another (carotid) artery again 30 s before the end of index isc. Infarct size (I) and area at risk (R) were delineated with the aid of TTC staining and green fluorescent microspheres respectively and their ratio was expressed in percent (%I/R). RESULTS: Remote local and remote distal postC reduced the % I/R ratio (17.7 +/- 1.7% and 18.4 +/- 1.6%, respectively vs 47.0 +/- 2.5% in the control group, P < 0.01). Classic PostC had an intermediate protective effect (33.1 +/- 1.7%, P < 0.05 vs all the other groups). CONCLUSION: Remote postconditioning consisted of 1 min isc/1 min rep protects the ischemic rabbit heart in vivo, independently of the site of the remote artery. This intervention seems to confer a stronger protection than the classic postconditioning.

Alternative pharmacological interventions that limit myocardial infarction.

Despite current optimal treatment, the morbidity and mortality of coronary heart disease remain significant worldwide and open the way for the development of novel cardioprotective therapies. In the last two decades, a remarkable scientific effort has focused on the limitation of infarct size. Important input from experimental studies has led the way in this direction. However, clinical and preclinical results using various cardioprotective strategies to attenuate reperfusion injury have generally not been applicable for every day clinical practice. Protection of the ischemic myocardium is known to occur as a result of ischemic preconditioning (PC), in which repetitive brief periods of ischemia protect the heart from a subsequent prolong ischemic insult. Although PC is a powerful form of protection, it is of limited clinical application for obvious ethical and practical reasons. Another endogenous form of cardioprotection, similar to PC but applicable at the time of reperfusion, termed postconditioning (PostC), has been recently described. Short series of repetitive cycles of brief reperfusion and re-occlusion of the coronary artery applied at the onset of reperfusion, reduce the infarct size and coronary artery endothelial dysfunction. At present, pharmacological PC and PostC are possible alternative methods that may substitute pharmaceutical treatments the short ischemic insults. Adenosine, nicorandil and other agents have been already used as pharmacological mimetics of ischemic PC in multicenter trials. We summarize the recent research efforts on novel therapeutic strategies and on the design of new compounds, based on the accumulated knowledge of the ligands, receptors and intracellular signaling pathways of PC and PostC.

Usefulness of inflammatory and haemostatic markers to predict short-term risk for death in middle-aged ischaemic stroke patients.

OBJECTIVES: There is increasing evidence that inflammation and hypercoagulability play an important role in the pathophysiology of acute ischaemic stroke. We examined the in-hospital prognostic value on mortality of C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), fibrinogen and D-dimer in middle-aged ischaemic stroke patients. MATERIALS AND METHODS: We recruited 231 consecutive patients <66 years with acute ischaemic stroke. CRP, TNF-alpha, fibrinogen and D-dimer levels were determined within 12 h from admission. RESULTS: Fifteen (6.5%) patients died during hospitalization. CRP, fibrinogen and D-dimer levels were significantly higher in patients who died compared with those who survived but only CRP and fibrinogen were independently associated with death, after adjusting for various confounding factors. For 1 mg/l increase in CRP there was a 20% higher risk of dying while for 10 mg/dl increase in fibrinogen the additive risk was 18%. CRP levels >18 mg/l and fibrinogen levels >490 mg/dl were the optimal points that discriminated those who died from the rest. CONCLUSIONS: CRP and fibrinogen levels can predict independently the risk of early death in middle-aged ischaemic stroke patients emphasizing the role of inflammation and coagulation in the evolution of ischaemic stroke.

Association of heart failure in homozygous beta-thalassemia with the major histocompatibility complex.

BACKGROUND: In beta-thalassemia major, heart failure primarily affecting left ventricular systolic function is the most common complication and cause of death. Apart from iron deposition, it has been recently reported that myocarditis might be another contributing factor in the pathogenesis of acute or chronic heart failure, acting possibly through an autoimmune mechanism. In an attempt to assess the role of immunogenetic factors in the development of heart failure associated with beta-thalassemia major, we studied the frequency of major histocompatibility antigens/alleles A, B, DR, and DQ in homozygous beta-thalassemic patients with and without heart failure primarily affecting the left ventricle. METHODS AND RESULTS: Forty-five consecutive unrelated Greek patients with homozygous beta-thalassemia and left-sided chronic heart failure were studied. Fifty-eight unrelated Greek patients with homozygous beta-thalassemia without heart failure and 130 unrelated Greek healthy controls were also studied. In all subjects, class I HLA-A and -B typing was performed by the complement-mediated lymphocytotoxicity assay, whereas class II HLA-DR and -DQ typing was performed by polymerase chain reaction. HLA-DRB1*1401 allele frequency was significantly increased in patients with beta-thalassemia major without left-sided heart failure compared with those with heart failure (corrected P [P(c)]=0. 02, odds ratio 0.1) and healthy controls (P(c)=0.001). HLA-DQA1*0501 allele frequency was increased in patients with heart failure compared with patients without heart failure (P(c)=0.04, odds ratio 14) and healthy controls (P(c)=0.004). CONCLUSIONS: Differences exist in the immunogenetic profile between homozygous beta-thalassemic patients with and without left-sided heart failure, raising the possibility that genetically defined immune mechanisms may play an important role in the pathogenesis of heart failure in beta-thalassemia.

Acute endothelin-A receptor antagonism prevents normal reduction of myocardial ischemia on repeated balloon inflations during angioplasty.

BACKGROUND: Myocardial ischemia and reperfusion are associated with increased production of endothelin (ET)-1. METHODS AND RESULTS: We examined the effects of BQ-123, a selective ET(A) receptor antagonist, in 80 patients. All patients were randomly allocated to an intracoronary infusion of saline or BQ-123 (6 micromol/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. CONCLUSIONS: Acute ET(A) 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.

Dobutamine echocardiographic study in patients with nonischemic dilated cardiomyopathy and prognostically borderline values of peak exercise oxygen consumption: 18-month follow-up study.

OBJECTIVES: We sought to study the prognostic value of dobutamine echocardiography in patients with nonischemic dilated cardiomyopathy (DCM) and prognostically borderline values of peak oxygen consumption (VO2max) during exercise. BACKGROUND: Changes in echocardiographic variables assessed by dobutamine echocardiography can be used to evaluate the functional status of patients with chronic heart failure (CHF) and DCM. METHODS: In 27 consecutive patients (mean age 55 +/- 15 years) with VO2max values between 10 and 14 ml/kg body weight per min, a low infusion rate (10 microg/kg per min) dobutamine echocardiographic test was performed. The induced changes in echocardiographic variables were measured, and an 18-month follow-up study was done. RESULTS: At the end of the protocol, 9 patients (group I) had died from cardiac reasons, whereas the remaining 18 patients (group II) survived. After dobutamine infusion, the left ventricular end-systolic diameter (LVESD) was smaller in group II (6.22 +/- 0.94 cm) than in group I (6.99 +/- 0.76 cm; p < 0.05), whereas end-systolic wall stress (ESWS) was higher in group I (1030.66 +/- 193.98 g/cm2) than in group II (691.57 +/- 297.06 g/cm2; p < 0.05). The changes in LVESD and ESWS were greater in group I (0.75 +/- 0.36 cm and 463.11 +/- 159.87 g/cm2, respectively) than in group II (-0.04 +/- 0.36 cm and 83.16 +/- 291.74 g/cm2, respectively; p < 0.01 for both). CONCLUSIONS: In the "gray" zone of VO2max, dobutamine echocardiography seems to be a valuable prognostic indicator in patients with CHF and DCM.

Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome.

OBJECTIVES: We sought to test the hypothesis that activation of the serotonergic system in patients with vasovagal syndrome during the head-up tilt test provokes syncope. BACKGROUND: Central serotonergic activation participates in the pathogenesis of neurocardiogenic syncope. Drugs increasing serotonin (5-HT) in the central nervous system have not been tested as drug challenges during the head-up tilt test with clomipramine (Clom-HUT). METHODS: The serotonergic re-uptake inhibitor clomipramine was infused (5 mg in 5 min) at the start of Clom-HUT in 55 patients (mean age 40 +/- 17 years) with a positive history of recurrent neurocardiogenic syncope and in 22 healthy control subjects (mean age 46 +/- 15 years). Blood samples were taken at 0, 5, 10 and 20 min for estimation of plasma prolactin and cortisol as neuroendocrine indicators of central serotonergic responsivity. All subjects had been previously tested with a basic 60 degrees head-up tilt test (B-HUT) for 30 min, and if negative, isoproterenol infusion was given at the end of the test. RESULTS: Twenty-nine (53%) of the 55 patients and none of the 22 control subjects had a positive result in the B-HUT. With Clom-HUT, the proportion of patients who experienced a positive response increased to 80% (n = 44), although this happened to only one control subject. Prolactin and cortisol plasma levels increased significantly in the positive Clom-HUT patient group only. CONCLUSIONS: The results indicate an increased responsivity of the central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion with the tilt test seems to considerably improve its diagnostic value.

Relationship between iNOS expression and aortic cell proliferation and apoptosis in an elastase-induced model of aorta aneurysm and the effect of 1400 W administration.

BACKGROUND: In the present study, we employed an elastase infusion-dependent abdominal aortic aneurysm (AAA) model to examine inducible nitric oxide synthase (iNOS) expression in relation to cellular proliferation and apoptosis in this pathologic condition. Furthermore, we employed N-(3-(aminomethyl)benzyl)acetamidine (1400 W), a previously shown selective iNOS inhibitor, to further explore this relationship. METHODS: Adult male Wistar rats were randomized into separate groups. Group A served as a control and received an intra-aortic saline infusion, while groups B, C, and D received an intra-aortic elastase infusion according to standard protocols. The animals in group C were administered postoperatively the highly selective iNOS inhibitor, 1400 W, while rats in group D received regularly the same compound preoperatively and postoperatively. The animals were killed at postoperative days 7 and 14. Aorta diameter and nitric oxide (NO), nitrite/nitrate, and MDA levels were measured. iNOS expression was assessed by immunohistochemistry and Western blot analysis, while Ki-67 immunohistochemistry and TUNEL assay were used to evaluate cellular proliferation and apoptosis, respectively. RESULTS: Increased iNOS and NO levels accompanied aneurysm development in groups B, C, and D, but these levels were significantly lower in groups C and D, compared with group B. Interestingly, very low but detectable levels of iNOS were found in the control group, indicating a basal constitutive level. Cell growth parameters were augmented in group B compared with group A. In contrast, groups C and D exhibited a significant decrease of the cellular growth parameters but did not attain normal values. CONCLUSIONS: iNOS-derived NO is associated with the cellular growth parameters of the vessel cells, predominantly smooth muscle cells. Selective iNOS blockage ameliorates the cellular remodeling in AAAs.

Increased risk for coronary heart disease in blue-collar workers at a military industrial plant in Greece?

OBJECTIVE: To test the hypothesis that blue-collar workers have a higher prevalence of risk factors for Coronary Heart Disease than white-collar workers. METHODS: A cross-sectional study of 262 employees (208 males, 54 females, mean age: 50,65 years) was made of a Greek military industrial plant. Blood samples were taken and analyzed for lipids, lipoprotein levels and glucose levels; arterial blood pressure and body mass index (BMI) were also recorded. Smoking habits were ascertained by the use of a self-administered questionnaire. RESULTS: White-collar workers had significantly higher mean levels of total and LDL cholesterol than blue-collar workers. No significant differences were found regarding arterial blood pressure, BMI, glucose, triglycerides and HDL cholesterol levels. Both groups reported similarly high rates of smoking. Multivariate analysis confirmed an independent association of abnormal levels of total and LDL cholesterol with white-collar occupation. CONCLUSION: These findings partly contradict the current pattern of CHD risk factors in Western workforces. Possible interpretations, as well as the limitations of the study, are discussed.

Assessment of the functional status of heart failure in non ischemic dilated cardiomyopathy: an echo-dobutamine study.

BACKGROUND: The functional status of heart failure (HF) is conventionally evaluated by peak exercise oxygen consumption (VO2 max). Dobutamine echocardiography can be used to evaluate myocardial reserve. The aim of this study was to estimate the functional status of chronic HF in patients with dilated cardiomyopathy, by investigating the changes in echo-variables, as assessed by echo-dobutamine, in relation with VO2 max. METHODS AND RESULTS: A low infusion rate echo-dobutamine test (10 micrograms/kg/min) was performed in 30 patients with dilated cardiomyopathy and 1 h later VO2 max was measured. VO2 max (ranging from 7.6 to 23 ml/kg/min, mean 14.06 +/- 0.64 ml/kg/min) was correlated with the changes (values obtained after inotropic stimulation minus those obtained at baseline) in left ventricular end-systolic diameter (r:0.80, p:0.001), in left ventricular end-systolic posterior wall thickness (r:0.73, p:0.001) and in left ventricular heart-rate corrected mean velocity of circumferential fiber shortening (Vcfc)/end-systolic meridional wall stress ratio (r:0.64, p:0.0001). A negative correlation was found between VO2 max and the changes in end-systolic meridional wall stress (r: -0.76, p:0.001). After dobutamine infusion Vcfc/systolic meridional wall stress ratio increased in patients with VO2 max > 14 ml/kg/min but decreased in patients with VO2 max < 14 ml/kg/min (0.0001 +/- 0.0001 vs -0.0002 +/- 0.0003 circ x cm2/g x s, p:0.0001). End-systolic meridional wall stress was decreased in patients with VO2 max > 14 ml/kg/min but increased in patients with VO2 max < 14 ml/kg/min (-126.97 +/- 34.24 vs 205.77 +/- 56.71 g/cm2, p:0.0001). CONCLUSION: The changes in echo-variables assessed by echo-dobutamine are well correlated with VO2 max and seem to be accurate for evaluating the functional status of chronic HF in patients with dilated cardiomyopathy.

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.

Preconditioning limits myocardial infarct size in hypercholesterolemic rabbits.

BACKGROUND: Hypercholesterolemia predisposes to coronary artery disease and causes endothelial dysfunction; some reports suggest that endothelial derived substances are involved in ischemic preconditioning. OBJECTIVE: Our aim was to examine the possibility that preconditioning maybe attenuated in a clinically relevant animal model of hypercholesterolemia with atherosclerosis. METHODS: Male rabbits were fed with cholesterol enriched diet and then divided into two groups (A and B) without and with preconditioning, respectively. A second series of rabbits fed a normal diet were similarly divided into two groups (C and D) without and with preconditioning, respectively. All the animals were subjected to 30 min ischemia and 180 min reperfusion. Blood samples were collected for cholesterol assessment; arterial and heart samples were harvested at the end for histopathological examination. Infarct (I) and risk areas (R) were delineated with Zn-Cd particles and TTC staining. RESULTS: Cholesterol in groups A and B was 58.3+/-8.7 mg% at baseline and 1402+/-125 mg% at 8 weeks (P<0.0001) and in groups C and D 57.5+/-5.8 mg% before the surgical procedure. I/R% was 39. 3+/-6.3% in group A, 16.7+/-3.9% in B (P<0.01), 41.4+/-7.5% in C and 10.8+/-3.3% in D (P<0.01). CONCLUSION: We conclude that preconditioning is unlikely to be attenuated by hypercholesterolemia.

Heart failure in beta thalassemia: a 5-year follow-up study.

PURPOSE: To evaluate the survival of patients with beta thalassemia and heart failure who were treated with iron chelation therapy. SUBJECTS AND METHODS: Fifty-two consecutive patients with beta thalassemia and heart failure were followed in a prospective 5-year study. All patients underwent a full clinical examination with chest radiograph, electrocardiogram, and echocardiographic investigation performed at 6-month intervals or when a new symptom developed. RESULTS: Of the 52 patients (mean [+/- SD] age, 24 +/- 5 years), 25 (48%) survived 5 years after the onset of heart failure. Forty-three patients had left-sided heart failure, and 9 had right-sided heart failure. Those with left-sided heart failure were younger at presentation with heart failure (22 +/- 4 years vs. 31 +/- 6 years; P <0.001), had lower ejection fractions (36% +/- 9% vs. 64% +/- 10%; P <0.001), and had a lower mean serum ferritin level (3355 +/- 1241 ng/mL vs. 6,397 +/- 1,613 ng/mL; P <0.001). CONCLUSION: The 5-year survival rate in patients with beta thalassemia with heart failure was greater than previously reported. There are clinical characteristics that may make patients more likely to develop left- or right-sided heart failure.

Effect of intracoronary estrogen on coronary collateral blood flow velocity.

The effect of estrogen on collateral circulation has not been previously investigated. We assessed the acute effect of estradiol on collateral blood flow velocity with the Flowire during percutaneous transluminal coronary angioplasty and found that intracoronary estradiol decreased collateral blood flow velocity compared with controls.

Estrogen replacement therapy and exercise performance in postmenopausal women with coronary artery disease.

We treated 10 postmenopausal women with stable angina, positive exercise test, and documented coronary artery disease with oral conjugated equine estrogen (0.625 mg/day of Premarin) or placebo for 4 weeks, in random order, with crossover after a 4-week washout period. Exercise tests, performed after each treatment period while the patients were taking their usual antianginal drugs showed no differences; thus, short-term estrogen does not improve exercise-induced ischemia compared with placebo.

Acute hemodynamic effects of estrogen administration in postmenopausal women.

The hemodynamic effects of estrogens in replacement doses have not been fully clarified; therefore, we studied the acute hemodynamic changes after 0.625 and 1.25 mg of conjugated estrogens, administered intravenously, using a thermodilution catheter, in postmenopausal women without structural heart disease. Pulmonary and systemic pressures and resistances and stroke volume did not change compared with baseline, but heart rate and cardiac output decreased significantly, which may be associated with estrogen's previously described calcium-blocking effect or with a more recently contemplated beta-blocking action.

Ablation therapy of type I atrial flutter may eradicate paroxysmal atrial fibrillation.

In patients with paroxysms of atrial fibrillation preceded by episodes of atrial flutter on Holter monitoring, eradication of the flutter circuit may also abolish the episodes of atrial fibrillation. At electrophysiology study, these patients are identified by documentation of simultaneous flutter of the right atrium and fibrillation of the left atrium.