Regulation of GADD153 induced by mechanical stress in cardiomyocytes.

BACKGROUND: Growth arrest and DNA damage-inducible gene 153 (GADD153), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of GADD153 in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of GADD153 expression and apoptosis induced by mechanical stress in cardiomyocytes. MATERIALS AND METHODS: Aorta-caval shunt was performed in adult Sprague-Dawley rats to induce volume overload. Rat neonatal cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles min(-1). RESULTS: The increased ventricular dimension measured using echocardiography in the shunt group (n = 8) was reversed to normal by treatment with chaperon 4-phenylbutyric acid (PBA) (n = 8) at 500 mg kg(-1) day(-1) orally for 3 days. GADD153 protein and mRNA were up-regulated in the shunt group when compared with sham group (n = 8). Treatment with PBA reversed the protein of GADD153 to the baseline values. The TUNEL assay showed that PBA reduced the apoptosis induced by volume overload. Cyclic stretch significantly increased GADD153 protein and mRNA expression after 14 h of stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA and tumour necrosis factor-alpha (TNF-alpha) antibody 30 min before stretch, reduced the induction of GADD153 protein. Stretch increased, while GADD153-Mut plasmid, SP600125 and TNF-alpha antibody abolished the GADD153 promoter activity induced by stretch. GADD153 mediated apoptosis induced by stretch was reversed by GADD153 siRNA, GADD153-Mut plasmid and PBA. CONCLUSIONS: Mechanical stress enhanced apoptosis and GADD153 expression in cardiomyocytes. Treatment with PBA reversed both GADD153 expression and apoptosis induced by mechanical stress in cardiomyocytes.

Myostatin expression in ventricular myocardium in a rat model of volume-overload heart failure.

BACKGROUND: Mechanical stress increases myocardial myostatin expression. However, the expression of myostatin in chronic heart failure resulting from volume-overload and after treatment with beta-blockers is little known. The authors hypothesize that myostatin plays a role in the failing myocardium because of volume-overload. MATERIALS AND METHODS: Aorto-caval shunt was created over a 4-week period in adult Sprague-Dawley rats to induce volume-overload heart failure. RESULTS: Heart weight and body weight ratio significantly increased after shunting. The left ventricular end-diastolic dimension also significantly increased. Treatment with carvedilol in the shunt group reversed the increase in heart weight and ventricular dimension to the baseline values. Myocardial and skeletal myostatin proteins were up-regulated in the shunt group. The mRNA of myocardial myostatin also increased in the shunt group. Treatment with carvedilol reversed both protein and mRNA of myocardial myostatin to the baseline values. Treatment with N-acetylcysteine and doxazosin partially decreased myostatin mRNA and protein expression as compared with the shunt group. Carvedilol normalized the increased immunohistochemical labelling of myocardial myostatin in the shunt group. CONCLUSION: Myocardial myostatin mRNA and protein expression were up-regulated in the rat model of volume-overload heart failure. Treatment with carvedilol is associated with a limitation of increased myostatin expression in the failing ventricular myocardium.

Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction.

BACKGROUND: Gene and stem cell therapies hold promise for the treatment of ischaemic cardiovascular disease. However, combined stem cell and angiogenic growth factor gene therapy for acute ischaemic myocardium has not been previously reported. This study hypothesized that combined stem cell and gene therapy would not only augment new vessels formation but also improve myocardial function in acute ischaemic myocardium. METHODS: Human angiopoietin-1 (Ang1) cDNA and VEGF(165) cDNA were ligated into AAV vector. The purified CD34(+) cells were obtained from human umbilical cord blood samples. Cord blood CD34(+) cells were transduced with AAV vector encoding either the human Ang1 (AAV-Ang1) or VEGF(165) (AAV-VEGF) cDNA alone, or both (AAV-Ang1 plus VEGF). Immediately after ligation of the left anterior descending coronary artery in male SCID mice, culture-expanded CD34(+) cells transduced with AAV-Ang1, AAV-VEGF or AAV-Ang1 plus VEGF were injected intramyocardially at the left anterior free wall. RESULTS: Western blot showed that Ang1 and VEGF protein expressions were enhanced in the CD34(+)cells transduced with AAV-Ang1 and AAV-VEGF, respectively. Infarct size significantly decreased and capillary density significantly increased after treatment with CD34(+)/AAV-Ang1 plus VEGF when compared with treatment by CD34(+) only. Combined therapy with CD34(+) and AAV-Ang1, CD34(+) and AAV-VEGF, CD34(+) and AAV-Ang1 plus VEGF, all showed significantly higher cardiac performance in echocardiography than the therapy with CD34(+) alone 4 weeks after myocardial infarction. CONCLUSIONS: Combined therapy with human umbilical cord blood CD34(+) cells and both Ang1 and VEGF genes reduced infarct size, attenuated the progression of cardiac dysfunction and increased capillary density in acute myocardial infarction in mice.

Immediate and long-term outcomes of stent implantation for unprotected left main coronary artery disease.

Left main coronary artery (LMCA) disease is now uniformly treated with coronary artery bypass grafting (CABG). However, some patients with LMCA disease do not receive CABG because of high operative risks. The advent of stent implantation has permitted a non-operative improvement in myocardial blood flow in many patients with single- and multi-vessel coronary artery disease. However, the outcomes of stent implantation for unprotected LMCA disease are still unclear. Stent implantation was performed for unprotected LMCA disease in 13 patients; eight patients had high operative risk and five patients had refused CABG. The primary success rate was 100% (13/13 patients). One patient (8%) developed a non-Q-wave myocardial infarction after LMCA stenting. Repeat angiography was obtained in five patients (38%) with recurrent angina, and three patients (23%) received repeated percutaneous transluminal coronary angioplasty (PTCA) for LMCA restenosis. In the follow-up period of 18+/-3 months, 12 patients (92%) remained in satisfactory condition with no further need for surgical intervention. One patient (8%) ultimately required CABG, and she died after CABG at 3 months after LMCA stenting. In conclusion, although CABG remains the standard treatment for LMCA disease, the present study demonstrates that stent implantation is a safe and clinically beneficial revascularization procedure for unprotected LMCA disease in patients who have high operative risk as well as those who refuse CABG.

Angiotensin II receptor antagonist blocks the expression of connexin43 induced by cyclical mechanical stretch in cultured neonatal rat cardiac myocytes.

Mechanical forces have profound effects on cardiomyocytes. To test whether angiotensin II is a potential mediator of stretch-induced effects on gap junctions, we used the angiotensin II (AT1) receptor antagonist, losartan, to investigate the cyclical stretch-induced expression of connexin43 (Cx43), the major cardiac muscle gap junction channel protein. Cultured neonatal rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles/min. The levels of Cx43 protein began to increase as early as 2 h after stretch was applied, reached a maximum of six-fold over the control by 24 h and remained at this level another 24 h (i.e. up to 48 h after stretch was applied). These increases of Cx43 protein at 24 h were largely (73%) and completely (100%) attenuated (P<0.001) by the addition (30 min before stretch) of 10 n M and 100 n M losartan, respectively. Similarly, the Cx43 mRNA levels in stretched cardiomyocytes rose 89% (P<0.01) above control (non-stretched cells) mRNA levels. This increase also was blocked by losartan. Cyclical stretch increased (and losartan decreased) the immunohistochemical labeling of Cx43 and significantly increased release of angiotensin II into the culture media from 7.5+/-0.6 ng/ml to 23.8+/-1.0 ng/ml (P<0.01) after a 1 h stretch. These findings indicate that cyclical mechanical stretch augments angiotensin II production and Cx43 gene expression in cultured cardiomyocytes, partially through mediation of the AT1 receptors, and suggests interaction between the cardiomyocyte local rennin-angiotensin system and Cx43 in response to stretch.

Cyclical mechanical stretching increases the expression of vascular endothelial growth factor in rat vascular smooth muscle cells.

BACKGROUND AND PURPOSE: Mechanical forces have profound effects on vascular smooth muscle cells (VSMCs). The mechanism by which mechanical stimuli regulate vascular endothelial growth factor (VEGF) expression and regulation has yet to be elucidated. We investigated the effect of cyclical mechanical stretching on regulation of the VEGF gene in VSMCs. MATERIALS AND METHODS: Cultured rat VSMCs grown on a flexible membrane base were stretched by applying a vacuum at 60 cycles/minute. VEGF concentration in the cultured media was determined by enzyme-linked immunoassay. VEGF gene expression was determined by Western blot and Northern blot. The location of VEGF in the VSMC was studied immunohistochemically. Chimeric constructs of the VEGF promoter were deleted and the promoter activity was determined by luciferase activity. RESULTS: VEGF concentration increased by 21 to 32% as early as 10 minutes after stretching and remained at this level for up to 12 hours. The concentration of VEGF reached a maximum of 2.8-fold over that in control cells by 2 hours after stretching and declined slightly thereafter. The amount of VEGF mRNA in stretched cells increased as early as 1 hour after stretching, reached a maximum of 3.2-fold over the amount in control cells by 2 hours, and remained at this level for up to 6 hours after stretching. Immunohistochemical study confirmed increased VEGF expression in VSMCs after stretching. Stretched cells transfected with a Sac-Nhe fragment showed only 46% of the luciferase activity of unstretched control cells. However, stretched cells transfected with chimeric plasmids containing a Spe-Nhe fragment showed 2.8-fold luciferase activity over that in control cells. CONCLUSIONS: Cyclical mechanical stretching upregulates expression of the VEGF gene in VSMCs at the transcription level. The VEGF 5'-flanking region contains a negative stretch-response element located in the 0.4-kb Sac-Pst fragment and a positive stretch-response element located in the 0.6-kb Spe-Sac fragment.

Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1alpha/VP16 hybrid transcription factor.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that regulates expression of genes involved in O(2) homeostasis, including vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis. We sought to exploit this native adaptive response to hypoxia as a treatment for chronic ischemia. METHODS AND RESULTS: A hybrid protein consisting of DNA-binding and dimerization domains from the HIF-1alpha subunit and the transactivation domain from herpes simplex virus VP16 protein was constructed to create a strong, constitutive transcriptional activator. After transfection into HeLa, C6, and Hep3B cells, this chimeric transcription factor was shown to activate expression of the endogenous VEGF gene, as well as several other HIF-1 target genes in vitro. The bioactivity of HIF-1alpha/VP16 hybrid gene transfer in vivo was examined in a rabbit model of hindlimb ischemia. Administration of HIF-1alpha/VP16 was associated with significant improvements in calf blood pressure ratio, angiographic score, resting and maximal regional blood flow, and capillary density (all P:<0.01). CONCLUSIONS: The HIF-1alpha/VP16 hybrid transcription factor is able to promote significant improvement in perfusion of an ischemic limb. These results confirm the feasibility of a novel approach for therapeutic angiogenesis in which neovascularization may be achieved indirectly by use of a transcriptional regulatory strategy.

Effects of norepinephrine on apoptosis in rat neonatal cardiomyocytes.

BACKGROUND AND PURPOSE: Norepinephrine (NE) is elevated in heart failure and can induce apoptosis in adult cardiac myocytes. However, it is not known whether NE can induce apoptosis in neonatal cardiac myocytes. This study examined the ability of NE to stimulate apoptosis in rat neonatal cardiac myocytes in vitro. METHODS: Neonatal rat cardiac myocytes were exposed to NE alone, NE + propranolol, or NE + prazosin for 24 hours. Apoptosis was assayed by DNA laddering with agarose gel electrophoresis and immunofluorescent terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Reverse transcription polymerase chain reaction was used to evaluate the expression of Mcl-1. Creatine kinase activity in the cultured medium was used as a measure of the toxicity of NE on myocytes. RESULTS: NE increased DNA laddering on agarose gel electrophoresis and increased the number of apoptotic cells in a dose-dependent manner. No increase in apoptosis was found in response to NE doses between 1 and 50 mumol/L. NE at concentrations of 100 to 400 mumol/L increased apoptosis from 10% to 31% of cells. The ability of NE to stimulate apoptosis in rat neonatal cardiac myocytes was completely blocked by propranolol, but not prazosin. NE treatment at high concentrations sharply reduced the level of Mcl-1 mRNA, coincident with the increase in the number of apoptotic cells. Creatine kinase activity in the cultured medium was similar among the controls and NE-treated myocytes. CONCLUSIONS: Our results showed that NE at high concentrations stimulated apoptosis in rat neonatal cardiac myocytes in vitro. Apoptosis induced by NE was associated with down-regulation of Mcl-1. However, NE at the same concentration was not toxic to rat neonatal cardiac myocytes.

Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb.

BACKGROUND: Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have recently been identified as ligands for the endothelial cell-specific Tie2 receptor. Little is known regarding the impact of these Tie2 ligands on postnatal neovascularization. Accordingly, we tested the hypothesis that gene transfer of plasmid DNA encoding Ang1 and Ang2 could modulate collateral vessel development in a rabbit model of hindlimb ischemia. METHODS AND RESULTS: pAng1* (n=15), pJFE control (no Ang1* insert) (n=9), pAng2 (n=9), pcDNA3 control (no Ang2 insert) (n=10), or saline (n=5) was injected intramuscularly into the rabbit ischemic hindlimb. Collateral vessel development and limb perfusion were assessed before and 30 days after treatment. Calf blood pressure ratio (ischemic to normal hindlimb) was increased 30 days after Ang1* gene transfer versus controls (Ang1*, 0.90+/-0.02; pJFE, 0.76+/-0.05; saline, 0.77+/-0. 03; P<0.05). Angiographic score was higher (P<0.05) in the pAng1* group (0.63+/-0.02) than in the pJFE (0.51+/-0.03) or saline (0. 52+/-0.02) group. Maximal (postpapaverine) blood flow in the ischemic limb was higher (P<0.05) after pAng1* (67.8+/-4.9 mL/min) than pJFE (51.2+/-4.4 mL/min) or saline (52.9+/-4.9 mL/min). Capillary density and capillary/muscle fiber ratio (242+/-12/mm2 and 0.89+/-0.06, respectively) were higher (P<0.01) with pAng1* than pJFE (172+/-11/mm2 and 0.64+/-0.05) or saline (166+/-10/mm2 and 0. 67+/-0.05). Neovascularization was not enhanced with pAng2. CONCLUSIONS: Ang1 but not Ang2 gene transfer produces anatomic and physiological evidence of enhanced collateral vessel formation. Ang1 may modulate neovascularization in adult animals and thus represents a feasible therapeutic strategy for patients with tissue ischemia. The role of Ang2 in postnatal neovascularization remains to be clarified.

A method to reduce response times in prehospital care: the motorcycle experience.

This study compared the response times of a motorcycle and a standard ambulance in a congested urban emergency medical services (EMS) setting. The study was performed in Taipei, Taiwan, a densely populated urban area. A basic life support (BLS) motorcycle (without defibrillation capability) and an advanced life support (ALS) ambulance were based at three study hospitals and simultaneously dispatched when there was a perceived need for ALS ambulance transport. Over a 3-month period, prehospital personnel evaluated 307 medical and trauma emergencies. Time data were insufficient for analysis in 33 cases, leaving a study population of 274. Response times of the motorcycle and the ambulance were prospectively assessed and compared. During rush hours, the response times of the motorcycle and ambulance were 4.9+/-3.0 minutes and 6.3+/-3.4 minutes (P < .05), respectively, and in non-rush hours, 4.2+/-2.1 minutes and 5.1+/-2.5 minutes (P < .05), respectively. Using motorcycles to transport EMTs to the emergency scene significantly reduced response time compared with a standard ambulance in a congested urban setting. Large prospective studies are required to determine the impact on patient outcome of shorter EMS response times using motorcycles. EMS motorcycles appear feasible and deserve consideration to help expedite prehospital care in other systems in densely populated cities.

Cardiac troponin T, creatine kinase, and its isoform release after successful percutaneous transluminal coronary angioplasty with or without stenting.

BACKGROUND: Cardiac troponin T is a sensitive and specific marker for the detection of minor myocardial injury. However, it has been rarely used to monitor myocardial injury after coronary stenting. The purpose of the study was to measure troponin T after apparently successful percutaneous transluminal coronary angioplasty (PTCA) with or without coronary stenting and to compare its result with serum creatine kinase and its isoform, CKMB. METHODS: The incidence of cardiac troponin T elevation was compared with that of creatine kinase or CKMB in 120 consecutive patients with symptomatic ischemia undergoing visually successful PTCA with (n = 59) or without stenting (n = 61). Troponin T, creatine kinase, and CKMB were measured before, immediately after, and 18 to 24 hours after the procedures were performed. RESULTS: No patient had abnormal troponin T, creatine kinase, or CKMB levels before and immediately after the procedures. Moreover, no patient showed electrocardiographic evidence of myocardial infarction. Troponin T was elevated in 17 patients at 18 to 24 hours after coronary stenting and in eight patients after PTCA. Both creatine kinase and CKMB were elevated in five patients after coronary stenting and in three patients after PTCA. The frequency of abnormal troponin T levels was significantly higher than that of creatine kinase or CKMB after coronary interventions (21% vs 6.7%; p < 0.01), and it was significantly higher after stenting when compared with angioplasty alone (29% vs 13%; p < 0.05). Patients with abnormal troponin T levels were more likely to undergo repeat revascularization than those without (24% vs 6%; p < 0.01). CONCLUSION: Cardiac troponin T is more sensitive than creatine kinase and CKMB in detecting minor myocardial injury after coronary interventions. The incidence of troponin T release is higher in the patients undergoing stent implantation than in patients treated with angioplasty alone.

Concentrations of serum interleukin-8 after successful cardiopulmonary resuscitation in patients with cardiopulmonary arrest.

To assess differences in serum interleukin-8 concentrations in resuscitated and nonresuscitated patients after cardiopulmonary resuscitation (CPR), and to compare changes of interleukin-8 levels with hemodynamic variables after restoration of spontaneous circulation, 39 patients with out-of-hospital cardiopulmonary arrest who had undergone CPR were studied. Venous blood samples were taken after CPR and 1 and 2 hours after restoration of spontaneous circulation to measure serum interleukin-8 levels by the enzyme-linked immunosorbent assay method. The median serum interleukin-8 levels after CPR were significantly higher in resuscitated than in nonresuscitated patients (64.9 pg/ml; range 30.2 to 1497 vs 0 pg/ml; range 0 to 31.6 pg/ml; p < 0.001). One and 2 hours after restoration of spontaneous circulation, the median serum interleukin-8 levels were 96.2 pg/ml and 155.4 pg/ml, respectively. Mean values of systolic blood pressure immediately after and 1 and 2 hours after restoration of spontaneous circulation were 117 +/- 9 mm Hg, 130 +/- 11 mm Hg, and 136 +/- 13 mm Hg, respectively. No significant correlations were found between hemodynamic values and serum interleukin-8 levels. In conclusion, successful initial resuscitation was associated with increased serum interleukin-8 concentrations. The interleukin-8 levels remained at high values 2 hours after restoration of spontaneous circulation.

Influence of additional partition on the recovery of atrial function after atrial compartment operation for atrial fibrillation.

Chronic atrial fibrillation can be eliminated by an atrial compartment operation, but additional partition on the right atrium impairs the recovery of right atrial mechanical function. Thus, it is important to appropriately divide the atria for both maintaining sinus rhythm and maximizing atrial mechanical function.

Serum levels of intercellular adhesion molecule-1 and E-selectin in patients with acute ischaemic stroke.

To investigate the role of circulating intercellular adhesion molecule-1 (ICAM-1) and E-selectin in ischaemic stroke, serum levels of ICAM-1 and E-selectin were measured by ELISA in 51 patients with acute ischaemic stroke within 24 h, and in 25 age-matched healthy controls and 10 young healthy volunteers. Carotid Doppler ultrasonography showed a significant stenosis (> 50%) of the carotid or vertebrobasilar artery in 11 of 51 stroke patients. Serum levels of ICAM-1 [mean (SE)] were higher (P < 0.01) in patients with ischaemic stroke [381 (30) ng/ ml] than in age-matched controls [271 (27) ng/ml] and young controls [246 (6) ng/ml]. There was no significant difference in serum E-selectin levels [mean (SE)] among stroke patients, age-matched and young controls [47 (6), 39 (3), and 41 (3) ng/ ml, respectively; P = NS]. The leucocyte count [mean (SD)] was higher (P < 0.01) in patients with ischaemic stroke [8310 (2800)] than in age-matched controls [6040 (930)]. Serum levels of ICAM-1 and E-selectin did not significantly differ between patients with or without abnormal carotid or vertebrobasilar artery disease. In conclusion, serum ICAM-1 level and leucocyte count were elevated in acute ischaemic stroke within 24 h, while the E-selectin level did not change significantly. This finding suggests that adhesion molecules may play an important role in the post-rolling process of leucocyte-endothelial cell interaction in acute ischaemic stroke.

Use of cardiac troponin T, creatine kinase and its isoform to monitor myocardial injury during radiofrequency ablation for supraventricular tachycardia.

To determine whether radiofrequency ablation for supraventricular tachycardia causes significant minor myocardial injury, 16 patients with supraventricular tachycardia undergoing radiofrequency ablation were studied. Cardiac troponin T, creatine kinase and its MB form (CKMB) were measured before, immediately after ablation and every 6 h thereafter for 24 h to detect myocardial injury. Elevation of creatine kinase, CKMB and cardiac troponin T was observed in 6, 4 and 5 patients, respectively. The peak mean creatine kinase concentration was 167 +/- 152 IU/l and that of CKMB was 9 +/- 6 IU/l. The peak mean cardiac troponin T level was 0.44 +/- 0.47 ng/ml. The frequency of elevated measurements was not statistically different among creatine kinase CKMB and cardiac troponin T. The mean pulse numbers of ablation, mean duration of ablation, radiofrequency current and mean total energy did not differ statistically between those with or without elevated cardiac troponin T. It was concluded that radiofrequency ablation for supraventricular tachycardia indeed caused some minor myocardial injury and the frequency of elevated cardiac troponin T was comparable to that of CKMB.

Circulating intercellular adhesion molecule-1 and E-selectin in patients with acute coronary syndrome.

To characterize the role of circulating intercellular adhesion molecules (ICAM-1) and E-selectin in patients with acute coronary syndrome, serum levels of ICAM-1 and E-selectin were measured by enzyme-linked immunosorbent assay (ELISA). Group 1 comprised 17 patients with acute myocardial infarction; group 2 included 17 patients with unstable angina; and group 3 included 19 control subjects. These 53 patients all had prolonged chest pain within 24 h and all underwent coronary angiography. Group 1 and 2 patients had significant coronary artery disease, while group 3 had normal coronary arteries. Blood samples were collected at the emergency department before antiplatelet agents were given. Serum levels of 1CAM-1 were higher in group 1 and 2 (383 +/- 27 and 337 +/- 11 ng/mL, respectively) as compared with group 3 (282 +/- 18 ng/mL) (group 1 vs 3, p<0.01; group 2 vs 3, p<0.05). The serum levels of ICAM-1 were not significantly different between group 1 and 2. Serum levels of E-selectin in group 1, 2, and 3 were 58 +/- 8, 51 +/- 4, and 58 +/- 5 ng/mL, respectively. The serum levels of E-selectin showed no significant difference among the three groups. In conclusion, serum levels of ICAM-1 were elevated in patients with acute coronary syndrome within 24 h, while the E-selectin levels did not change significantly. This finding suggests that adhesion molecule may play an important role in the postrolling process of leukocyte-endothelial cell interaction in acute coronary syndrome.

Low-serum, high-density lipoprotein cholesterol concentration is an important coronary risk factor in Chinese patients with low serum levels of total cholesterol and triglyceride.

The significance of low-serum high-density lipoprotein concentrations (<35 mg/dl) with respect to coronary atherogenesis in Chinese patients with low levels of total serum cholesterol (<200 mg/dl) and triglycerides (<250 mg/dl) was assessed. Persons with such a lipid profile pattern were still at high risk, and high-density lipoprotein. like smoking, appeared to be the most predictive independent coronary risk factor.

Diagnostic accuracy of transesophageal echocardiography for detecting patent ductus arteriosus in adolescents and adults.

To compare the accuracy of transesophageal echocardiography (TEE) with that of transthoracic echocardiography (TTE) in the detection of patent ductus arteriosus (PDA) in the adolescent and the adult, 40 patients with PDA and 50 patients with other congenital heart diseases were studied. All echocardiograms were recorded before cardiac catheterization and surgery. The echocardiographic diagnosis of PDA was made by direct visualization of a shunt flow in the duct. A mosaic flow in the pulmonary artery without direct visualization of the duct was considered possible but not definitely diagnostic of PDA. TEE showed greater sensitivity and negative predictive value than TTE (97% vs 42%, and 98% vs 68%, respectively; p < 0.001) in confirming the diagnosis of PDA. The specificity and positive predictive value in establishing the diagnosis of PDA were the same for both techniques. In the subgroup of patients with Eisenmenger's syndrome, the sensitivity of TEE and TTE in confirming diagnosis of PDA was 100% and 12% (p < 0.01), respectively. The sensitivity of monoplane and biplane TEE in the diagnosis of PDA was comparable (95% and 100%, respectively; p = NS). In conclusion, TEE was highly sensitive and specific in detecting PDA in adolescents and adults. It was also highly valuable for detecting the cause of pulmonary hypertension in patients with Eisenmenger's syndrome.

Transesophageal echocardiographic assessment of mitral valve position and pulmonary venous flow during cardiopulmonary resuscitation in humans.

BACKGROUND: The mechanisms of blood flow during closed-chest cardiopulmonary resuscitation (CPR) in humans have been debated since the technique was first described in 1960. Two competing models, the cardiac pump theory and the thoracic pump theory, have been proposed, and some investigators have used mitral valve position during the downstroke of chest compression to distinguish between them. Previous studies using either transthoracic or transesophageal echocardiography have yielded conflicting results, and there have been few, if any, hemodynamic or echocardiographic studies on pulmonary venous flow (PVF) during CPR. METHODS AND RESULTS: In this study, transesophageal two-dimensional and pulsed Doppler echocardiography were used to study mitral valve position and flow, together with PVF, in 20 adult patients undergoing manual CPR. In the 17 patients who could be analyzed, the mitral valve closed in 5 patients (group 1) during chest compression but stayed open or opened further in the remaining 12 patients (group 2). Peak forward mitral flow occurred during the release phase in group 1 but during the compression phase in group 2. During chest compression, PVF occurred in the forward direction (from the pulmonary vein to the left atrium) in 8 of the group 2 patients (group 2a) and in the backward direction (from the left atrium to the pulmonary vein) in all group 1 patients and the remaining 4 patients in group 2 (group 2b). The downtime (time from collapse to CPR) was significantly shorter (P < .05) for those in group 1 (7.0 +/- 4.4 minutes) than in groups 2a (19.8 +/- 7.7 minutes) and 2b (17.8 +/- 6.8 minutes). CONCLUSIONS: Transesophageal echocardiography performed during manual CPR in humans disclosed three different patterns of mitral valve position and PVF during chest compression. The presence of an opened mitral valve with forward mitral flow and backward pulmonary venous flow during chest compression in a small number of subjects underscores this heterogeneity in blood flow and suggests the possible existence of a "left atrium pump" in addition to the currently known "left ventricle pump" and "chest pump" mechanisms.