bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of vascular runoff on myointimal hyperplasia after mechanical balloon or thermal laser arterial injury in dogs.
Authors: Hehrlein C , Chuang C H , Tuntelder J R , Tatsis G P , Littmann L , Svenson R H
Published: June 2012

BACKGROUND

Clinical evidence suggests that poor vascular runoff reduces the long-term success rate of femoral angioplasty procedures. The purpose of this experimental study was to examine myointimal hyperplasia of dog femoral arteries after balloon denudation, thermal laser arterial injury, or sham operation in normal and reduced vascular runoff conditions.

METHODS AND RESULTS

Before mechanical balloon injury or transluminal heated laser probe motion, the peripheral vascular runoff of dogs was reduced by ligating the femoral artery below its three distal side branches, decreasing the femoral flow rate from 114 +/- 9 to 52 +/- 5 ml/min (mean +/- SEM). Endothelial denudation with a predominantly intact elastic internal membrane and circumferential structural changes in the media were noted by light microscopy 1 hour after balloon injury. Focal completely necrotic lesions of intima and media were found 1 hour after thermal laser arterial injury. After 8 weeks, the maximal thickness of neointima plus media of the site of previous intervention was greater after balloon injury (0.45 +/- 0.03 mm) and thermal laser injury (0.54 +/- 0.03 mm) than after sham operation (0.40 +/- 0.01 mm; p less than 0.001) in normal runoff dogs. Reduced vascular runoff augmented myointimal hyperplasia both in the balloon-injured and thermally damaged arteries; the wall thickness increased from 0.45 +/- 0.03 to 0.93 +/- 0.10 mm and from 0.54 +/- 0.03 to 0.65 +/- 0.05 mm, respectively (p less than 0.001). The neointimal and medial wall area of the balloon-injured arteries contributed 48% to the area encompassed by the external elastic membrane compared with an 81% portion when vascular runoff was reduced (p less than 0.01). A 47% neointimal and medial wall area was found in thermally injured arteries with normal runoff compared with 63% after runoff reduction (p less than 0.05).

CONCLUSION

This study suggests that hemodynamic factors associated with poor vascular runoff play an important role in extending myointimal hyperplasia independent of method and severity of the arterial injury during angioplasty.
Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study.
Authors: Bassand J P , Cassagnes J , Machecourt J , Lusson J R , Anguenot T , Wolf J E , Maublant J , Bertrand B , Schiele F
Published: June 2012

BACKGROUND

Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study.

METHODS AND RESULTS

One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died.

CONCLUSIONS

The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications.
Light and electron microscopic localization of brain natriuretic peptide in relation to atrial natriuretic peptide in porcine atrium. Immunohistocytochemical study using specific monoclonal antibodies.
Authors: Hasegawa K , Fujiwara H , Itoh H , Nakao K , Fujiwara T , Imura H , Kawai C
Published: June 2012

BACKGROUND

Although first isolated from the porcine brain, brain natriuretic peptide (BNP) is also found in the heart, particularly in the atria.

METHODS AND RESULTS

We examined the immunocytochemical localization of BNP in relation to atrial natriuretic peptide (ANP) in five porcine atria using highly specific monoclonal antibodies. With the use of an indirect immunoperoxidase method, serial sections examined by light microscopy showed foci of multihormonal myocytes containing both ANP and BNP localized in the subendocardium. Monohormonal myocytes containing ANP only were observed in the subepicardium and part of the subendocardium. The staining intensity of ANP and BNP showed a transmural gradient from the subendocardium to the subepicardium. At the electron microscopic level, double immunocytochemistry using a two-face immunogold-staining method revealed two types of granules: Type 1 is a monohormonal granule containing ANP alone, and type 2 is a multihormonal granule containing both ANP and BNP. Although most atrial myocytes contained both, type 1 granules were frequently observed in the epicardial side, and type 2 granules were frequently observed in the endocardial side. We observed a few type 2 granules even in the light microscopically monohormonal myocytes.

CONCLUSIONS

These data suggest that the atrial myocyte population comprises single, multipotential cells able to synthesize both natriuretic peptides in varying proportions. The atrial transmural gradient of BNP and ANP may be related to responses to wall stress.
Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model.
Authors: Kaplan A V , Leung L L , Leung W H , Grant G W , McDougall I R , Fischell T A
Published: June 2012

BACKGROUND

Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis.

METHODS AND RESULTS

In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin.

CONCLUSIONS

At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters.
Relation of early hemodynamic changes to final cardiac phenotype and survival after neural crest ablation in chick embryos.
Authors: Tomita H , Connuck D M , Leatherbury L , Kirby M L
Published: June 2012

BACKGROUND

Microcinephotography was used to study a model of persistent truncus arteriosus created in chick embryos by ablation of premigratory neural crest destined for the third and fourth aortic arch arteries as well as the septum of the cardiac outflow tract.

METHODS AND RESULTS

Twenty-five control embryos and 105 of 202 experimental embryos were filmed on day 3 of incubation and then reincubated. The remaining 97 experimental embryos were not filmed because of twisting of the embryos, but they were reincubated. There was no difference in either the survival rate (p greater than 0.23) from day 3 to day 11 of incubation or the incidence of persistent truncus arteriosus (p greater than 0.08) between the filmed and the nonfilmed embryos. Incomplete looping of the cardiac tube observed in experimental embryos during early cardiogenesis correlated with a right ventricular origin of the outflow vessels in the definitive heart. Hemodynamic measurements indicated that there was no difference in heart rate, ejection fraction, systolic and diastolic areas, stroke volume, and cardiac output between controls and the experimental group as a whole. However, embryos that did not survive to day 11 had decreased stroke volume (p less than 0.001) and cardiac output (p less than 0.001), whereas embryos that survived to day 11 with cardiac malformations had increased stroke volume and cardiac output in early embryogenesis.

CONCLUSIONS

Increased stroke volume and cardiac output may be necessary factors for survival in embryos with cardiac dysmorphogenesis and probably are associated with dilation of the ventricular portion of the cardiac tube, which leads to malalignment of the outflow vessel or vessels.
A lesson from the controversy about heart rate adjustment of ST segment depression.
Authors: Bobbio M , Detrano R
Published: June 2012

To summarize the literature review, the heart rate adjustment appears to be able to perfectly discriminate patients with different numbers of diseased coronary vessels in one center, to increase the diagnostic accuracy of three-vessel or left main disease in eight centers, and unable to improve accuracy in seven centers. To explain those differences, several methodological and statistical biases have been considered. However, a recent report regarding the application of the method in eight centers and a meticulous literature review could not explain the superior performance in some laboratories.
A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice.
Authors: Bargiggia G S , Tronconi L , Sahn D J , Recusani F , Raisaro A , De Servi S , Valdes-Cruz L M , Montemartini C
Published: June 2012

BACKGROUND

Imaging of the flow convergence region (FCR) proximal to a regurgitant orifice has been shown to provide a method for quantifying the regurgitant flow rate. According to the continuity principle, the FCR is constituted by concentric hemispheric isovelocity surfaces centered at the orifice. The flow rate is constant across all isovelocity surfaces and equals the flow rate through the orifice. For any isovelocity surface the flow rate (Q) is given by: Q = 2 pi r2 Vr, where 2 pi r2 is the area of the hemisphere and Vr is the velocity at the radial distance (r) from the orifice.

METHODS AND RESULTS

We studied 52 consecutive patients with mitral regurgitation (mean age, 49 years; age range, 21-66 years) verified by left ventricular angiography using color flow mapping. The FCR r was measured as the distance between the first aliasing limit--at a Nyquist limit obtained by zero-shifting the velocity cutoff to 38 cm/sec--and the regurgitant orifice. Seven patients without evidence of an FCR had only grade 1+ mitral regurgitation angiographically. There was a significant relation between the Doppler-derived maximal instantaneous regurgitant flow rate and the angiographic degree of mitral regurgitation in the other patients (rs = 0.91, p less than 0.001). The regurgitant flow rate by Doppler also correlated with the angiographic regurgitant volume (r = 0.93, SEE = 123 ml/sec) in the 15 patients in normal sinus rhythm and without other regurgitant lesions in whom it could be measured. The correlation between regurgitant jet area within the left atrium and the angiographic grade was only fair (rs = 0.75, p less than 0.001).

CONCLUSIONS

Color flow Doppler provides new velocity information about the proximal FCR in patients with mitral regurgitation. According to the continuity principle, the maximal instantaneous regurgitant flow rate, obtained with the FCR method, may provide a quantitative estimate of the severity of mitral regurgitation, which is relatively independent of technical factors.
Ultrasonic energy. Effects on vascular function and integrity.
Authors: Fischell T A , Abbas M A , Grant G W , Siegel R J
Published: June 2012

BACKGROUND

Ultrasonic energy transmitted via flexible wire probes provides a new means of ablating atherosclerotic plaque. We studied the effects of ultrasonic energy (20 kHz) delivered via a ball-tipped wire probe on arterial vasomotor behavior in rabbit thoracic aortas in a perfused whole-vessel model.

METHODS AND RESULTS

After precontraction with phenylephrine (10(-5) M) or KCl (60 mM), the effects of ultrasonic energy (0.7-5.5 W x 60 seconds, 42-330 J) on arterial vasomotor behavior were measured using long-axis ultrasonic vessel imaging of the proximal (ultrasonic probe-treated) and distal (untreated) control segments. The efficacy of plaque ablation at these same probe-tip power outputs was evaluated in atherosclerotic, human cadaver iliofemoral arteries. Ultrasonic energy caused dose (energy)-dependent relaxation in rabbit aortas after precontraction with phenylephrine in arteries with endothelium (n = 8) and without endothelium (n = 8) (p less than 0.001 versus ultrasound treated at power outputs of 2.9 and 5.5 W). There was no difference in the relaxation dose responses between endothelialized and endothelially denuded segments (p = NS). Ultrasonic energy also caused significant relaxation (67 +/- 8%) after voltage-dependent precontraction with 60 mM KCl. Temperature measurements revealed less than 1 degrees C warming of the vessel wall during as long as 2 minutes of treatment at a power output of 5.5 W. Pathological examination showed no smooth muscle injury at (moderate) power outputs that caused arterial relaxation. At probe-tip power outputs of 2.9-5.5 W, ultrasonic energy recanalized two of two totally occluded cadaveric iliofemoral vessel segments. The ultrasonic ablation catheter was also demonstrated to cause arterial relaxation in a recanalized canine femoral artery in vivo.

CONCLUSIONS

Ultrasonic energy delivered via a flexible-wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. At moderate power outputs, this relaxation response does not appear to be due to thermal effects or irreversible smooth muscle cell injury. This vasorelaxant effect of ultrasonic energy is also apparent in vivo, at doses that effectively ablate atherosclerotic plaque, and may improve the safety of arterial recanalization using ultrasonic energy.
Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias.
Authors: Brugada J , Boersma L , Kirchhof C , Allessie M
Published: June 2012

BACKGROUND

The goal of this study was to investigate the nature and electrophysiological mechanisms of the proarrhythmic effects of flecainide in Langendorff-perfused rabbit hearts.

METHODS AND RESULTS

A thin layer of epicardium was obtained by an endocardial cryotechnique in 10 Langendorff-perfused rabbit hearts. Six other hearts were kept intact. Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide. During control, in the thin layer of epicardium, application of one to three premature stimuli induced nonsustained ventricular tachycardia in out of 10 hearts, and burst pacing induced nonsustained ventricular tachycardia in four hearts and sustained ventricular tachycardia in two hearts. During administration of 1 microgram/ml flecainide, application of one to three premature stimuli induced sustained ventricular tachycardia in five hearts, and burst pacing induced sustained ventricular tachycardia in nine hearts. All tachycardias were based on circus movement of the impulse around arcs of functional block. During administration of flecainide, different locations of the arc of block could be found in the same heart, leading to different reentrant circuits with different cycle lengths. In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide.

CONCLUSIONS

Flecainide alters propagation of the impulse in thin surviving layers of myocardium in a manner that facilitates the induction of functionally determined reentry.
Psychological factors related to prehospital delay during acute myocardial infarction.
Authors: Kenyon L W , Ketterer M W , Gheorghiade M , Goldstein S
Published: June 2012

BACKGROUND

Prior studies have had difficulty identifying factors that significantly explain patients' delay in responding to symptoms of acute myocardial infarction (AMI).

METHODS AND RESULTS

We therefore examined factors affecting the time between symptom onset and hospital arrival for 103 AMI patients admitted to a Detroit metropolitan hospital between October 1989 and January 1990. Variables evaluated included demographic and medical history factors, psychological characteristics of somatic and emotional awareness, and type A behavior. The mean prehospital delay time was 9.0 +/- 10.8 hours (median, 5.0 hours; range, 0.25-62.0 hours). Delay time was not significantly associated with demographic or medical history categories or with type A behavior. Of study variables that can be identified prior to evolution of an AMI, somatic and emotional awareness were the only factors significantly predictive of delay time. Patients who were more capable of identifying inner experiences of emotions and/or bodily sensations sought treatment significantly earlier than patients with low emotional or somatic awareness (low emotional awareness median delay, 12.8 hours; high emotional awareness median delay, 3.8 hours; low somatic awareness median delay, 7 hours; high somatic awareness median delay, 4 hours).

CONCLUSIONS

Variations in sensitivity to bodily sensations and emotions appear to play an important role in treatment seeking and thus potentially in treatment outcome for AMI patients. Assessment of these characteristics in patients with coronary risk factors could allow early identification of persons at risk of excessive delay in responding to symptoms of AMI.
Responses of atherosclerotic human coronary arteries in vivo to the endothelium-dependent vasodilator substance P.
Authors: Crossman D C , Larkin S W , Dashwood M R , Davies G J , Yacoub M , Maseri A
Published: June 2012

BACKGROUND

The effects of the endothelium-dependent vasodilator substance P (SP) on atherosclerotic human coronary arteries was studied.

METHODS AND RESULTS

[125I]-SP binding to luminal cells was shown to be preserved in the atherosclerotic epicardial coronary arteries of four patients. No binding to medial smooth muscle cells was demonstrated. Intracoronary infusions of SP were undertaken in patients with coronary artery disease. SP was infused for 2-minute periods starting at a dose of 2.8 pmol/min rising by doubling increments to 22.4 pmol/min. Analysis of the epicardial coronary artery diameter, using a computerized analysis system (CAAS) of the angiograms, was performed at the end of each infusion. Analysis of seven smooth vessel segments from seven coronary vessels, which were stenosed at more proximal sites, was performed. Significant dose-dependent dilatation was seen (p = 0.04), which was maximal at 5.6 pmol/min SP. No additional dilatation was produced with 2 mg intracoronary isosorbide dinitrate (ISDN). Two of these seven patients showed no response to SP, and only one of these appeared to sustain dilatation with ISDN (2 mg intracoronary). In a second group of six patients with discrete coronary stenoses, analysis at the site of the stenosed segments appeared to reveal dilatation in response to SP in only one instance. One other stenotic segment dilated with isosorbide dinitrate but failed to dilate with SP; the remaining four were fixed. The segment immediately proximal to the stenosis preserved a dose-dependent vasodilator response.

CONCLUSIONS

These findings demonstrate that the endothelium-dependent vasodilator substance P can still produce epicardial vasodilatation in vivo in the presence of coronary atherosclerosis.
Growth of the great vessels in the normal human fetus and in the fetus with cardiac defects.
Authors: Ursell P C , Byrne J M , Fears T R , Strobino B A , Gersony W M
Published: June 2012

BACKGROUND

There is a paucity of quantitative anatomic data regarding human great vessel development that could be useful as a reference for fetal echocardiographers who must distinguish abnormal from normal cardiac development at early stages.

METHODS AND RESULTS

To determine normal growth patterns, we plotted the diameters of the aortic and pulmonary valves, ductus arteriosus, aortic isthmus, and descending aorta in 274 autopsy specimens from nonselected spontaneous abortuses of normal karyotype. There was a linear increase in the diameters of these structures within the developmental period studied (10-26 weeks). A relative narrowing of the aorta at the isthmus compared with the aortic valve and descending aorta probably indicates that the majority of fetal left heart output goes to the developing heart and brain. In contrast to previous studies of late gestation and neonatal animals, however, we found that the diameter of the aortic isthmus was larger than that of the ductus arteriosus, suggesting substantial isthmic blood flow in these midtrimester fetuses. Among nineteen other hearts with diverse defects, both of two hearts with a narrow isthmus had an enlarged ductus arteriosus and one heart with pulmonary atresia/intact septum had a narrow ductus and increased aortic valve diameter.

CONCLUSIONS

During midgestation, the normal heart may have substantial aortic isthmic blood flow that diminishes due to rerouting in late gestation when increased requirements of the fetal brain and other organs prevail. Although fetal shunts may explain some vessel abnormalities, the majority of cardiac defects in this study were not associated with abnormal growth of the great vessels within this developmental age range.
Radiation exposure during radiofrequency catheter ablation of accessory atrioventricular connections.
Authors: Calkins H , Niklason L , Sousa J , el-Atassi R , Langberg J , Morady F
Published: June 2012

BACKGROUND

Catheter ablation of accessory atrioventricular (AV) connections has been demonstrated to be effective in more than 85% of patients. One of the risks of this procedure is radiation exposure during the fluoroscopic imaging necessary to guide catheter manipulation. The objective of the present study was to measure the radiation received by patients and physicians during radiofrequency catheter ablation and to estimate the resultant somatic and genetic risks.

METHODS AND RESULTS

Radiation exposure to patients and physicians was measured during attempts at radiofrequency catheter ablation of accessory AV connections in 31 consecutive patients. Radiation exposure was measured using thermoluminescent sensors placed on the patient and on the physician. Somatic and genetic risks were estimated based on the radiation levels recorded using these sensors. The durations of fluoroscopy and of the catheter ablation procedure were recorded for each patient. Catheter ablation was successful in 28 of 31 patients (90%). Mean +/- SD duration of fluoroscopy was 44 +/- 40 minutes. The largest patient radiation dose was measured over the ninth vertebral body posteriorly (median, 7.26 rem [roentgen equivalents man]; range, 0.31-135.7 rem). Median radiation dose to the thyroid was 0.46 rem (range, 0.06-7.26 rem), and median radiation dose to the posterior iliac crest was 2.43 rem (range, 0.01-8.3 rem). The greatest radiation dose to the operator was recorded at the left hand (99 mrem). Mean radiation dose to the operator's eyes was 28 mrem.

CONCLUSIONS

Radiofrequency catheter ablation of accessory AV connections may result in significant radiation exposure to the patient and to the physician. Each hour of fluoroscopic imaging is associated with a lifetime risk of developing a fatal malignancy of 0.1% and a risk of a genetic defect of 20 per 1 million births. Although these risks must be recognized, they are relatively small compared with the risks associated with alternate approaches to management, including no therapy, antiarrhythmic drug therapy, and surgery.
Antithrombotic effects of combining activated protein C and urokinase in nonhuman primates.
Authors: Gruber A , Harker L A , Hanson S R , Kelly A B , Griffin J H
Published: June 2012

BACKGROUND

We have determined in vivo the relative antithrombotic efficacy and hemostatic safety of combining low-dose activated protein C (APC) and urokinase (urinary plasminogen activator, u-PA), two natural proteins that regulate thrombogenesis.

METHODS AND RESULTS

To model acute thrombotic responses of native blood under conditions of arterial flow, thrombogenic segments of Dacron vascular graft (VG) were incorporated into chronic exteriorized femoral arteriovenous (AV) access shunts in baboons. Thrombus formation on VG was determined by measuring 1) the deposition of autologous 111In platelets using real-time scintillation camera imaging, 2) the accumulation of 125I fibrin, 3) segment patency by Doppler flow analysis, and 4) blood tests for thrombosis, including plasma concentrations of platelet factor 4, beta-thromboglobulin, fibrinopeptide A (FPA), and D-dimer. Treatments consisting of low-dose and intermediate-dose APC (0.07 or 0.25 mg/kg.hr), u-PA (25,000 or 50,000 IU/kg.hr), or the combination were administered for 1 hour by continuous intravenous infusion. In untreated controls, platelets and fibrin accumulated rapidly, reaching plateau values at 1 hour of 15.1 +/- 3.8 x 10(9) platelets and 7.8 +/- 2.2 mg fibrin. Although the low-dose APC or u-PA alone did not decrease either platelet or fibrin deposition significantly, this combination moderately reduced both platelet and fibrin accumulation (7.3 +/- 2.6 x 10(9) platelets, p less than 0.05; 3.9 +/- 0.6 mg fibrin, p less than 0.05). Furthermore, intermediate-dose APC or u-PA reduced thrombus formation by half when administered alone (p less than 0.001 for both platelet and fibrin deposition), and the combination markedly interrupted the accumulation of platelets (3.0 +/- 1.0 x 10(9) platelets, p less than 0.001) and fibrin (1.3 +/- 0.6 mg fibrin, p less than 0.001). During active treatments, all VG segments remained patent. Hemostatic plug forming capability, as measured by template bleeding times, remained normal during all experiments (p greater than 0.05). The T50 clearance time for APC activity was not affected by the concurrent administration of u-PA. u-PA alone increased the plasma levels of D-dimer, FPA, and, interestingly, APC, implying that during pharmacological activation of the fibrinolytic system, thrombin activity was released, and the protein C pathway was activated.

CONCLUSIONS

A combination of intermediate-dose APC and u-PA produce substantial and efficient antithrombotic effects without impairing hemostatic function.
Cardiovascular and endocrine effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations in conscious dogs.
Authors: Donckier J E , Hanet C , Berbinschi A , Galanti L , Robert A , Van Mechelen H , Pouleur H , Ketelslegers J M
Published: June 2012

BACKGROUND

Increased plasma concentrations of endothelin-1, a potent vasoconstrictor produced by the endothelium, have been reported in various pathological conditions. This study was conducted to evaluate effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations.

METHODS AND RESULTS

Endothelin-1 was infused at increasing doses (2.5, 5, 10, and 20 ng/kg.min for 1 hour each) in nine conscious dogs. During endothelin-1 infusion, plasma endothelin-1 rose from a basal value of 1.8 +/- 0.4 pmol/l to 5.8 +/- 1.1 (pathophysiological), 20.8 +/- 3.9 (pathophysiological), 85.4 +/- 18.9 (pharmacological), and 311.4 +/- 55.7 (pharmacological) pmol/l at each dose, respectively. Heart rate increased at 2.5 ng/kg.min (from 129 +/- 7 to 146 +/- 12 beats/min) but decreased at 20 ng/kg.min (97 +/- 7 beats/min) (p less than 0.001). Such a biphasic response was also observed for peak (+)dP/dt and (dP/dt)/DP40 (p less than 0.005). Left ventricular systolic pressures, mean aortic pressure, and left atrial pressure increased over time (p less than 0.05, p less than 0.005, and p less than 0.001, respectively). The time constant of early isovolumic relaxation rose progressively (p less than 0.001). The percent systolic shortening decreased at 10 and 20 ng/kg.min (p less than 0.005). Pressure-segment length loops showed a reduction in systolic shortening associated with an increase in left ventricular systolic pressure at 20 ng/kg.min. Atrial natriuretic factor rose after 5 ng/kg.min from 28.5 +/- 6.5 to 92.0 +/- 18.2 pmol/l (p less than 0.005). Angiotensin II and catecholamines did not change significantly. Serum urea and creatinine rose progressively (p less than 0.05), whereas glucose decreased (p less than 0.05). The above results differed significantly from measurements obtained in a time-control group of six dogs.

CONCLUSIONS

A fourfold increase of plasma endothelin-1 obtained after doubling the infusion rate suggests a reduction in endothelin-1 clearance or endothelin-1 endogenous production. The biphasic response of heart rate is consistent with baroreflex-mediated effects resulting from vasodilation at the pathophysiological level and vasoconstriction at the pharmacological level. Hemodynamic data suggest an increase followed by a decrease in contractility at both levels, respectively. Finally, endothelin-1 is a stimulator of atrial natriuretic factor.
Does myocardial stunning contribute to infarct size limitation by ischemic preconditioning?
Authors: Miura T , Goto M , Urabe K , Endoh A , Shimamoto K , Iimura O
Published: June 2012

BACKGROUND

The mechanism through which ischemic preconditioning causes cardioprotection is unknown. The present study investigated the role of stunning in preconditioning.

METHODS AND RESULTS

We studied three different protocols of preconditioning: two cycles of 2-minute ischemia separated by 5-minute reperfusion (2'PC), one cycle of 5-minute ischemia by 5-minute reperfusion (5'PC1), and two cycles of 5-minute ischemia separated by 5-minute reperfusion (5'PC2). In the first series of experiments, the stunning associated with 2'PC, 5'PC1, or 5'PC2 was assessed using an epicardial Doppler transducer in anesthetized open-chest rabbits. The thickening fraction (percent baseline) of the preconditioned region was 76.8 +/- 7.2% (mean +/- SEM) after 2'PC but 31.4 +/- 9.2% and 34.3 +/- 9.7% after 5'PC1 and 5'PC2, respectively, which were significantly lower, thus indicating more severe stunning than that after 2'PC. In the second series of experiments, a branch of the left circumflex artery was occluded for 30 minutes and then reperfused for 72 hours in four groups of rabbits. One group was not preconditioned and three groups were preconditioned with 2'PC, 5'PC1, or 5'PC2 protocols before the 30-minute ischemia. In contrast to the differences observed in the stunning in the first series of experiments, histological infarct size was similar in the three preconditioned groups (21.1 +/- 3.0% of area at risk after 2'PC, 20.1 +/- 3.4% after 5'PC1, 16.4 +/- 4.2% after 5'PC2), all of which were significantly smaller than that in the unpreconditioned group (43.9 +/- 5.0%). The third series of experiments examined the degree of stunning by 2'PC, 5'PC1, or 5'PC2 and the size of infarct (tetrazolium staining) in the same animal after 30-minute ischemia/3-hour reperfusion; again, the results showed no significant correlation between degree of stunning and infarct size.

CONCLUSIONS

The myocardial infarct size-limiting effect of preconditioning did not correlate with the degree of myocardial stunning accompanying preconditioning. Thus, it is unlikely that myocardial stunning contributes to the cardioprotective effect of ischemic preconditioning.
Epicardial potential mapping. Effects of conducting media on isopotential and isochrone distributions.
Authors: Green L S , Taccardi B , Ershler P R , Lux R L
Published: June 2012

BACKGROUND

Epicardial excitation sequences, recovery sequences, and potential distributions are recorded from patients during surgery and from animals in the research laboratory for a variety of purposes. During such recordings, a portion of the cardiac surface is exposed to air, and the remainder of the epicardial surface variably is in contact with conductive tissue. No systematic studies document the degree to which these different conditions affect measured excitation times, potential distributions, and/or the configuration of epicardial electrograms.

METHODS AND RESULTS

Epicardial potential distribution was recorded from five isolated, perfused hearts using a 64-unipolar-lead sock. Data were recorded first with the heart suspended in air and then with the heart immersed in a heated tank filled sequentially to full and half-full levels with conductive Tyrode's solution and then NaCl-sucrose solution. These solutions had resistivity less than and more than that of blood, respectively, and air was assumed to have infinite resistivity. Epicardial potentials were recorded from two hearts before removal from the chest, both with and without a latex sheet insulating the heart from the pericardial cradle. Amplitude of recorded potentials from both intact and isolated hearts was markedly higher when the heart was surrounded by an insulating medium, but locations of positive and negative regions were less affected by surrounding medium. Isochrone activation maps calculated using the minimum derivative of the QRS (intrinsic deflection) were not affected by the conductivity of media surrounding the heart.

CONCLUSIONS

The present study provides evidence that isochrone maps recorded at surgery are not distorted by exposure of the cardiac surface to insulating air. Results suggest that epicardial isochrones recorded during cardiac surgery could be used in patients to assess the accuracy of "inverse" procedures that noninvasively compute epicardial electrograms and isochrones from body surface potentials.
Blood pressure control by the renin-angiotensin system in normotensive subjects. Assessment by angiotensin converting enzyme and renin inhibition.
Authors: Kiowski W , Linder L , Kleinbloesem C , van Brummelen P , Bühler F R
Published: June 2012

BACKGROUND

The participation of the renin-angiotensin system in the control of blood pressure in normal, sodium-replete subjects is not clear. The use of a specific inhibitor of human renin should allow a better delineation of the importance of this system.

METHODS AND RESULTS

Blood pressure responses were measured 1 hour after randomized, double-blind administration of the renin inhibitor Ro 42-5892 (600 mg p.o.) or the angiotensin converting enzyme inhibitor captopril (50 mg p.o.) in 20 healthy men on an ad libitum sodium diet. Effective inhibition of the renin-angiotensin system by either compound was indicated by increases of immunoreactive renin associated with an increase of angiotensin I production rate of 67.8 +/- 33.6% after captopril and a decrease of 79.5 +/- 16.4% after Ro 42-5892. Furthermore, Ro 42-5892 decreased plasma renin activity by 64%. Whereas intra-arterial diastolic (60 +/- 5.1 to 51.4 +/- 7.2 mm Hg, p less than 0.01) and mean arterial (77.7 +/- 6.0 to 71.4 +/- 8.5 mm Hg, p less than 0.001) pressures decreased after captopril, they remained unchanged after Ro 42-5892. Captopril, but not Ro 42-5892, increased forearm blood flow (2.4 +/- 0.8 versus 1.9 +/- 0.8 ml/min/100 ml, p less than 0.01) and significantly enhanced the increase of forearm blood flow to brachial artery infusions of bradykinin (0.15, 1.5, 5, 15, and 50 ng/min/100 ml; 5 minutes each) from 744 +/- 632% to 1,383 +/- 514% (p less than 0.01). Furthermore, repeat bradykinin infusions resulted in further decreases of blood pressure (from mean pressure of 71.4 +/- 8.5 to 63.2 +/- 7.6 mm Hg, p less than 0.01) only after captopril. Changes of blood pressure after captopril were unrelated to baseline plasma renin activity but correlated with captopril-induced enhancement of vasodilation to bradykinin (r = 0.68, p less than 0.05).

CONCLUSIONS

The lack of blood pressure effects of renin inhibition in contrast to angiotensin converting enzyme inhibition suggests that the renin-angiotensin system does not contribute significantly to blood pressure control in normotensive, sodium-replete subjects. The hypotensive activity of angiotensin converting enzyme inhibitors may result from additional hormonal effects, for example, inhibition of bradykinin degradation and/or subsequent increases of vasodilating prostaglandins or endothelium-derived relaxing factor(s).
Percutaneous transluminal coronary angioplasty of chronic total occlusions. Primary success, restenosis, and long-term clinical follow-up.
Authors: Ivanhoe R J , Weintraub W S , Douglas J S , Lembo N J , Furman M , Gershony G , Cohen C L , King S B
Published: June 2012

BACKGROUND

Angioplasty of chronically totally occluded vessels has been associated with a success rate well below and restenosis rate well above that for angioplasty of stenosed segments. However, long-term clinical outcome after successful revascularization of a chronically totally occluded vessel has not been reported in detail.

METHODS AND RESULTS

Accordingly, data for 480 patients undergoing angioplasty for chronic total occlusion at Emory University Hospital, Atlanta, Ga., from 1980 to 1988 were analyzed for predictors of in-hospital procedural and clinical (procedural success and absence of in-hospital complications) success, restenosis, and 4-year clinical follow-up. The study population was grouped by procedural and clinical success and failure. The groups were then compared for outcome, both in hospital and long term. The initial clinical success rate was 66% (317 of 480 patients). Independent correlates of failure were the number of vessels diseased (p less than 0.001), vessel location of the lesion (p = 0.016), and absence of any distal antegrade filling (p = 0.002). Follow-up data revealed 98% cardiac survival and 96% overall survival at 4 years for the group as a whole. Freedom from myocardial infarction or cardiac death was significantly greater in patients with clinical success (93%) than with clinical failure (89%, p = 0.0044). In the successful group, 87% were free from coronary surgery after 4 years compared with 64% in the failure group (p less than 0.0001). Two thirds of the patients were free of angina at last follow-up. The presence of angina at follow-up was the same for patients successfully treated and for those with failed angioplasty, which may be related to the frequent use of coronary surgery in the failure group.

CONCLUSIONS

In well-selected cases, the success rate for angioplasty of chronic total occlusion is acceptable. Furthermore, long-term clinical benefit is suggested by the high freedom from coronary surgery, myocardial infarction, and death in the patients who underwent successful revascularization.
Two-dimensional echocardiographic phase analysis. Its potential for noninvasive localization of accessory pathways in patients with Wolff-Parkinson-White syndrome.
Authors: Kuecherer H F , Abbott J A , Botvinick E H , Scheinman E D , O'Connell J W , Scheinman M M , Foster E , Schiller N B
Published: June 2012

BACKGROUND

In patients with the preexcitation syndrome who are undergoing transcatheter or surgical ablation, accurate localization of accessory pathways is critical. Because preexcitation is known to alter ventricular activation sequence and result in focal areas with presystolic contraction, we investigated whether phase analysis applied to two-dimensional echocardiographic cine loops objectively identifies these focal areas and can be used to localize ventricular insertion sites of accessory pathways.

METHODS AND RESULTS

We prospectively obtained phase images in 17 patients (11 males; age range, 11-35 years) during minimal preexcitation in normal sinus rhythm and during maximal preexcitation induced by right atrial pacing. A group of 11 normal subjects (six men; age range, 26-37 years) served as controls. Pathway locations predicted from phase imaging were compared with those predicted from routine 12-lead ECGs, from visual inspection of cine loop images, and from catheter-mounted electrode endocardial mapping. Cross-sectional views in a digital cine loop format were mathematically transformed using a first harmonic Fourier algorithm to obtain the corresponding phase images. Phase angle histograms were derived in eight wall segments. Mean and earliest phase angles were derived by computer analysis to quantitate contraction sequence. We found that during right atrial pacing, phase angles in focal areas markedly deviated from normal--mean phase angles from 33 degrees to 164 degrees, and earliest phase angles from 50 degrees to 180 degrees. Accessory pathways could be precisely localized in 53% of the patients by 12-lead ECG, in 59% by visual inspection of cine loop images, in 82% by phase imaging, and in 94% by a combination of the three methods.

CONCLUSIONS

Our results suggest that phase imaging, especially when used in combination with cine loop and 12-lead ECG, can be used to localize ventricular insertion sites of accessory pathways and may be clinically useful as a noninvasive adjunct to endocardial mapping in patients with Wolff-Parkinson-White syndrome.
Preventive administration of intravenous N-acetylcysteine and development of tolerance to isosorbide dinitrate in patients with angina pectoris.
Authors: Boesgaard S , Aldershvile J , Poulsen H E
Published: June 2012

BACKGROUND

Development of tolerance to organic nitrates may be related to depletion of sulfhydryl groups in vascular smooth muscle. N-Acetylcysteine (NAC), a sulfhydryl donor, has been reported to potentiate the effect of nitroglycerin and reverse tolerance in humans. However, its ability to prevent or delay the development of nitrate tolerance in patients with angina pectoris has not been established.

METHODS AND RESULTS

Ten patients with stable angina pectoris were treated with intravenous isosorbide dinitrate (ISDN; 5 mg/hr) combined with NAC (2 g i.v. over 15 minutes followed by 5 mg/kg/hr) or matching placebo for 30 hours in a double-blind, randomized, crossover study with a washout interval of 8 days. Bicycle exercise tests were performed before and at 1 1/2, 8, 20, 24, and 30 hours after start of treatment. After 24 hours of infusion, exercise parameters were not significantly different from pretreatment values (p greater than 0.05) during ISDN plus placebo, indicating development of tolerance to ISDN. In contrast, time to onset of angina, time to 1-mm ST segment depression, and total amount of ST segment depression were still significantly improved after 24-hour infusion of ISDN plus NAC (p less than 0.05). In addition, compared with placebo, a significant difference (p less than 0.05) in favor of NAC was observed regarding time to angina (507 +/- 63 versus 445 +/- 69 seconds, mean +/- SEM), time to 1-mm ST segment depression (435 +/- 43 versus 407 +/- 45 seconds), and total ST segment depression (1.8 +/- 0.9 versus 3.1 +/- 0.4 mm).

CONCLUSIONS

These results suggest that infusion of high doses of NAC in combination with ISDN for 30 hours affects and partially prevents the development of tolerance to antianginal effects normally observed during infusion with ISDN.
Frequency domain measures of heart period variability and mortality after myocardial infarction.
Authors: Bigger J T , Fleiss J L , Steinman R C , Rolnitzky L M , Kleiger R E , Rottman J N
Published: June 2012

BACKGROUND

We studied 715 patients 2 weeks after myocardial infarction to establish the associations between six frequency domain measures of heart period variability (HPV) and mortality during 4 years of follow-up.

METHODS AND RESULTS

Each measure of HPV had a significant and at least moderately strong univariate association with all-cause mortality, cardiac death, and arrhythmic death. Power in the lower-frequency bands--ultra low frequency (ULF) and very low frequency (VLF) power--had stronger associations with all three mortality end points than power in the higher-frequency bands--low frequency (LF) and high frequency (HF) power. The 24-hour total power also had a significant and strong association with all three mortality end points. VLF power was the only variable that was more strongly associated with arrhythmic death than with cardiac death or all-cause mortality. In multivariate Cox regression models using a step-up approach to evaluate the independent associations between frequency domain measures of heart period variability and death of all causes, ULF power was selected first (i.e., was the single component with the strongest association). Adding VLF or LF power to the Cox regression model significantly improved the prediction of outcome. With both ULF and VLF power in the Cox regression model, the addition of the other two components, LF and HF power, singly or together, did not significantly improve the prediction of all-cause mortality. We explored the relation between the heart period variability measures and all-cause mortality, cardiac death, and arrhythmic death before and after adjusting for five previously established postinfarction risk predictors: age, New York Heart Association functional class, rales in the coronary care unit, left ventricular ejection fraction, and ventricular arrhythmias detected in a 24-hour Holter ECG recording.

CONCLUSIONS

After adjustment for the five risk predictors, the association between mortality and total, ULF, and VLF power remained significant and strong, whereas LF and HF power were only moderately strongly associated with mortality. The tendency for VLF power to be more strongly associated with arrhythmic death than with all-cause or cardiac death was still evident after adjusting for the five covariates. Adding measures of HPV to previously known predictors of risk after myocardial infarction identifies small subgroups with a 2.5-year mortality risk of approximately 50%.