bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of myocardial reperfusion with echo planar magnetic resonance imaging. Discrimination between occlusive and reperfused infarctions.
Authors: Saeed M , Wendland M F , Yu K K , Lauerma K , Li H T , Derugin N , Cavagna F M , Higgins C B
Published: June 2012

BACKGROUND

The current treatment of many cases of acute myocardial infarction involves the use of thrombolytic agents. Evaluation of this therapy requires determination of the success of reperfusion and assessment of the presence and extent of infarction in the reperfused territory. The present study was designed to simulate in rat models several possible outcomes of reperfusion therapy: (1) successful reperfusion and absence of myocardial infarction, (2) successful reperfusion and presence of myocardial infarction, and (3) unsuccessful reperfusion. The usefulness of contrast-enhanced fast magnetic resonance (MR) imaging in defining the success of reperfusion was investigated. The dynamic effects were examined of low and high doses of gadolinium-BOPTA/dimeglumine (Gd-BOPTA/dimeg) on myocardial signal using MR inversion recovery echo planar imaging (IR-EPI) and gradient recalled echo planar imaging (GR-EPI), respectively.

METHODS AND RESULTS

Rats were subjected to one of the following regimens: reperfused reversible myocardial injury (n = 9), reperfused irreversible myocardial injury (n = 9), and occlusive infarction (n = 9). MR echo planar images were acquired every 1 or 2 seconds before, during, and after administration of Gd-BOPTA/dimeg. In all groups, normal myocardial signal was sharply increased on IR-EPI and decreased on GR-EPI at the peak of the bolus, followed by a gradual decline to baseline. In animals subjected to reperfused reversible myocardial injury, normal and previously ischemic regions were indistinguishable during and after the passage of Gd-BOPTA/dimeg. On the other hand, enhancement of reperfused irreversibly injured myocardium was delayed but increased steadily to a higher level than normal myocardium on IR-EPI. The reperfused irreversibly injured myocardium was identified on IR-EPI as a zone of high signal (hot spot). On GR-EPI, signal loss in reperfused irreversibly injured myocardium was significantly less compared with normally perfused myocardium. In animals with occlusive infarctions, there was no change in signal intensity over the ischemic region on either IR-EPI or GR-EPI. Occlusive infarction was identified as zones of either low (cold spot) or high (hot spot) signal compared with normal myocardium, depending on MR pulse sequence and dose of the contrast medium.

CONCLUSIONS

The transit of Gd-BOPTA/dimeg monitored by fast MR imaging techniques can be used to distinguish between reperfused reversibly and reperfused irreversibly injured myocardium and between occlusive and reperfused infarctions.
Prevalence of hypertension in Mexico City and San Antonio, Texas.
Authors: Haffner S , González Villalpando C , Hazuda H P , Valdez R , Mykkänen L , Stern M
Published: June 2012

BACKGROUND

Few data are available on the prevalence of hypertension in Mexico.

METHODS AND RESULTS

We compared the prevalence of mild hypertension (systolic blood pressure > or = 140 mm Hg and/or diastolic blood pressure > or = 90 mm Hg and/or use of antihypertensive medications) in 1500 low-income Mexican Americans who participated in the San Antonio Heart Study and 2280 low-income Mexicans who participated in the Mexico City Diabetes Study. The crude prevalence of mild hypertension was 17.1% in Mexican men versus 24.4% in Mexican American men (P = .001) and 17.4% in Mexican women versus 22.0% in Mexican American women (P = .005). After adjustment for age, body mass index (BMI), waist-to-hip ratio (WHR), non-insulin dependent diabetes mellitus (NIDDM), educational attainment, and percent native American genetic admixture (Caucasian and native American), the odds ratio (Mexico City/San Antonio) was 0.55 (95% CI, 0.39, 0.77; P < .001) in men and 0.81 (CI, 0.54, 1.12; P = .201) in women. In a pooled model including both men and women, the odds ratio was 0.67 (95%, CI, 0.53, 0.84; P < .001). In the pooled model, city, age, female sex, NIDDM, BMI, WHR, and low educational attainment were significantly related to the prevalence of hypertension.

CONCLUSIONS

The causes for these differences in hypertension prevalence are not known but may reflect a less modernized lifestyle in Mexico City, including greater physical activity, less obesity, and the consumption of a high-carbohydrate, low-fat diet.
Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK)
Authors: Neuhaus K L , von Essen R , Tebbe U , Jessel A , Heinrichs H , Mäurer W , Döring W , Harmjanz D , Kötter V , Kalhammer E
Published: June 2012

BACKGROUND

Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction.

METHODS AND RESULTS

Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin (70 IU/kg body wt bolus and 15 IU.kg-1.h-1) or hirudin (0.4 mg/kg body wt bolus and 0.15 mg.kg-1.h-1) infused over 48 to 72 hours and adjusted to an activated partial thromboplastin time of 2 to 3.5 times baseline values. In a pilot phase, 1000 patients receiving front-loaded alteplase for thrombolysis were to be recruited by 93 German centers. After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group. Other major bleeding occurred in five versus three patients and ventricular rupture occurred in three versus one patient in the hirudin and heparin groups, respectively. There were 19 in-hospital deaths, with 13 of them from the hirudin group.

CONCLUSIONS

Although the number of patients was too small for a definite benefit-risk assessment, at the dosage tested, hirudin in combination with front-loaded alteplase and aspirin may be associated with an increased rate of intracranial hemorrhage. Our findings are consistent with the observations of the GUSTO-II and TIMI-9 trials, where higher doses of another recombinant hirudin were used. Therefore, the therapeutic range of hirudin as an adjunct to thrombolysis may be smaller than previously thought, and reappraisal of dose finding should be considered.
Beneficial effects of metoprolol treatment in congestive heart failure. Reversal of sympathetic-induced alterations of immunologic function.
Authors: Maisel A S
Published: June 2012

BACKGROUND

Little information is available to explain why beta-blockers are beneficial in certain patients with congestive heart failure (CHF). Since catecholamines alter immune function, we asked whether beta-blocker treatment leads to enhancement of immune function.

METHODS AND RESULTS

Fifteen patients with New York Heart Association class III-IV CHF secondary to dilated cardiomyopathy were titrated to a minimum dose of metoprolol 25 mg BID on a background therapy of digoxin, diuretic, and angiotensin-converting enzyme inhibitors. Cardiac and immunologic studies were done before and 6 months to 1 year after treatment. While these patients served as their own controls, an additional population of patients with heart failure was followed for a similar time period on traditional medications. A panel of seven delayed hypersensitivity skin tests were placed at 6- to 12-month intervals on the patient's forearm. Seventy percent of all CHF patients were anergic (unable to respond to more than 1 antigen). The 30% who could respond averaged 2.2 antigens. After treatment with metoprolol, only 20% remained anergic (P < .001). The 80% of responders averaged 4.2 antigens (P < .001). Additionally, patients treated with metoprolol had an increased percentage of T cells, natural killer cells, and increased interleukin-2 receptor density upon stimulation with concanavalin A. These changes correlated to increases in ejection fraction. Patients not treated with metoprolol remained anergic and had no beneficial immunologic changes.

CONCLUSIONS

It appears that patients with dilated cardiomyopathy who are treated with metoprolol have enhancement of cell-mediated immunity and improvement of T-cell function; these improvements are correlated to improvement in ejection fraction.
New aspects in ultrasound-guided compression repair of postcatheterization femoral artery injuries.
Authors: Schaub F , Theiss W , Heinz M , Zagel M , Schömig A
Published: June 2012

BACKGROUND

This study was undertaken to expand the understanding of ultrasound-guided compression repair (UGCR) of postcatheterization femoral artery injuries.

METHODS AND RESULTS

In a series of 62 patients with pseudoaneurysms (n = 53) or arteriovenous (AV) fistulas (n = 9), UGCR was performed as a nonsurgical method in the treatment of postcatheterization femoral artery injuries. When the communicating channel could be visualized (43 cases), pressure was focused on it; otherwise (10 cases) the extraluminal cavity itself was compressed. In 45 cases, the elimination of flow in the pseudoaneurysm and/or the communicating channel could be achieved only with simultaneous temporary complete occlusion of the femoral artery. UGCR was successfully performed in 25 of 27 cases of false aneurysms (93%) in patients without anticoagulation and in 14 of 26 patients (54%) on anticoagulants. Three of 9 AV fistulas could be repaired by this method. No apparent correlation could be found between the therapeutic success and the size of the pseudoaneurysm or the age of the lesion.

CONCLUSIONS

In patients on anticoagulants and in patients with AV fistulas, the detection of a communicating channel that could be obliterated by direct mechanical compression was discerned as a discriminant factor of success.
Characterization of ATP-induced vasodilation in the human forearm vascular bed.
Authors: Rongen G A , Smits P , Thien T
Published: June 2012

BACKGROUND

Animal data indicate that ATP derived from aggregating thrombocytes or endothelium induces an endothelium-dependent vasodilator response that is mediated by P2y-purinergic receptors and is reduced when high dosages are administered. This reduced vasodilator response to high ATP doses has been associated with the concomitant release of endothelium-derived contracting factors. In contrast to the endothelium-dependent vasodilator response, ATP as released from sympathetic nerve endings induces a P2x-purinergic receptor-mediated vasoconstrictor response that may contribute to the attenuated vasodilator response to high dosages of luminally applied ATP. The dual action of ATP might be important in the pathophysiology of disease states characterized by an impaired endothelial function and increased thrombocyte aggregation. This study was performed to characterize the vascular response to ATP in humans.

METHODS AND RESULTS

The brachial artery was cannulated in 50 healthy male volunteers (age, 18 to 44 years) for drug infusion and measurement of mean arterial pressure. Forearm blood flow was recorded by venous occlusion strain-gauge plethysmography. ATP induced a dose-dependent vasodilator response that was significantly higher than the effect of equimolar adenosine infusion and that was not reduced by concomitant infusion of the P1-purinergic receptor antagonist theophylline. The infusion of the NO synthase antagonist NG-monomethyl-L-arginine (L-NMMA) reduced the average fall in forearm vascular resistance (FVR) to acetylcholine (-59 +/- 6% [mean +/- SEM] versus -42 +/- 8%; P < .05; N = 10) but did not affect the vasodilator response to ATP (-68 +/- 3% versus -64 +/- 6%; P > .1; N = 10) or sodium nitroprusside (SNP; -53 +/- 3% versus -49 +/- 4%; P > .01; N = 6). The L-NMMA-induced increase in FVR appeared to be related to the type of vasodilator pretreatment, being 94.7 +/- 16.7%, 44.9 +/- 8.7%, and 40.8 +/- 7.3% for acetylcholine, ATP, and SNP pretreatment, respectively (P < .01 for acetylcholine versus ATP and SNP; P > .1 for ATP versus SNP). In contrast to animal data, high dosages of intra-arterially infused ATP (up to 1000 micrograms.100 mL forearm-1.min-1) did not reveal a reduction in the forearm vasodilator response but appeared to be similar to the maximal forearm vasodilation as observed during postocclusive reactive hyperemia.

CONCLUSIONS

These observations indicate that ATP induces a potent dose-dependent vasodilator response that is not mediated by P1-purinergic receptor stimulation or by the release of nitric oxide. Moreover, in healthy volunteers, the vasodilator response to high intra-arterial dosages of ATP is not reduced by the release of endothelium-derived contracting factors or by the stimulation of P2x-purinergic receptors on the smooth muscle cells.
Platelet-induced vascular smooth muscle cell proliferation is modulated by the growth amplification factors serotonin and adenosine diphosphate.
Authors: Crowley S T , Dempsey E C , Horwitz K B , Horwitz L D
Published: June 2012

BACKGROUND

Platelet-mediated mechanisms have been implicated in intimal lesion formation following vascular injury. Although the participation of peptide growth factors has been suspected in this process, little has been known about the possible mitogenic role of other platelet factors that are released at sites of vascular injury.

METHODS AND RESULTS

We tested the hypothesis that platelet products, which are not peptide growth factors, are important modulators of the platelet-induced smooth muscle cell (SMC) proliferative response by acting as growth amplification factors. In these studies, cell proliferation was assessed by [3H]thymidine incorporation, flow cytometry, and direct cell counting. We examined the potential mitogenicity of several platelet products, including serotonin, ADP, norepinephrine, histamine, platelet-activating factor, the thromboxane A2 mimetic U46619, and bradykinin. Of the platelet products tested, serotonin and ADP induced a synergistic response with peptide growth factors. This synergy was greatest at low growth-factor concentrations. Addition of nonaggregated platelets to quiescent SMC cultures strongly stimulated cell proliferation. Since the addition of suramin to platelet-treated cultures markedly inhibited SMC proliferation, peptide growth factors are most likely the primary mitogens mediating this response. However, platelet-induced proliferation was also markedly reduced by the serotonin antagonists ketanserin and LY53857 (44%), and by the ADP antagonist apyrase (35%).

CONCLUSIONS

Therefore, serotonin and ADP contribute significantly, in synergy with peptide growth factors, to the platelet-induced SMC proliferative response. We propose that in vivo serotonin and ADP act as amplification factors for SMC proliferation at sites of vascular injury.
An angiotensin II receptor antagonist reduces myocardial damage in an animal model of myocarditis.
Authors: Tanaka A , Matsumori A , Wang W , Sasayama S
Published: June 2012

BACKGROUND

Recently, an angiotensin-converting enzyme inhibitor was shown to have a beneficial effect on virus-induced myocardial injury. We investigated the effect of a new angiotensin II type 1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-1H-benz imi dazole-7- carboxylate (TCV-116), in an animal model of viral myocarditis induced by encephalomyocarditis virus.

METHODS AND RESULTS

Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. TCV-116 (in 5% gum arabic) was given 1 day before (1 or 10 mg/kg) or 2 days after virus inoculation (0.3 or 3 mg/kg). Control mice received the vehicle only. All drugs were administered orally on a daily basis, and the animals were killed on day 14. When treatment was started 1 day before inoculation, the survival of mice receiving 10 mg/kg of TCV-116 improved (17 of 20 [85%] versus 14 of 22 [64%] control mice), but the difference was not significant. Heart weight (106 +/- 24 mg versus 133 +/- 33 mg, P < .05), histological scores for myocardial necrosis (1.1 +/- 0.3 versus 2.3 +/- 1.2, P < .01), cellular infiltration (1.4 +/- 0.7 versus 2.6 +/- 1.3, P < .05), and calcification (1.1 +/- 0.3 versus 2.1 +/- 1.1, P < .01) were significantly decreased in mice given TCV-116 at 3 mg/kg compared with the vehicle control mice. The plasma angiotensin II level was significantly higher in infected mice than in noninfected mice (71.8 +/- 30.2 versus 31.8 +/- 22.5 pg/mL, P < .05). TCV-116 did not inhibit viral replication in the heart.

CONCLUSIONS

This study suggests that angiotensin II plays an important pathophysiological role in viral myocarditis. Treatment with TCV-116, an angiotensin II receptor antagonist, had a cardioprotective effect.
Plasma triglycerides and three lipoprotein cholesterol fractions are independent predictors of the extent of coronary atherosclerosis.
Authors: Drexel H , Amann F W , Beran J , Rentsch K , Candinas R , Muntwyler J , Luethy A , Gasser T , Follath F
Published: June 2012

BACKGROUND

The lipoprotein system has manifold links to atherosclerotic disease. LDL cholesterol is related to lesion formation and growth. The cholesterol of HDLs is indicative of protection against atherosclerosis. The status of triglycerides and of subfractions of high-density lipoproteins as risk factors is less certain. Also, the magnitude of the atherogenic/protective power of these factors is not known.

METHODS AND RESULTS

Five hundred patients (418 men and 82 women) were enrolled in an angiographic study. A total of 1006 coronary lesions with > or = 50% narrowing were recorded as study end points. By extent of atherosclerosis, defined as the number of > or = 50% lesions, the study subjects were allocated to one of four ordered categories with 0, 1 to 3, 4 to 6, or 7 to 10 lesions, respectively. Subfractions of HDL cholesterol were determined by a dual precipitation method. By a polychotomous logistic regression model, it was found that, besides age and sex, LDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, and triglycerides were independently predictive (P < .05) of the extent of coronary atherosclerosis. An increase in age by 10 years was associated with an increase of the odds ratio for falling into a higher-extent category by a factor of 1.64, and the same increase of the odds ratio was obtained by increasing LDL cholesterol by 0.92 mmol/L or triglycerides by 1.01 mmol/L and by decreasing HDL2 cholesterol by 0.20 mmol/L or HDL3 cholesterol by 0.46 mmol/L. The less sensitive coronary end point, presence of atherosclerosis (ie, observation of > or = 1 lesion of > or = 50%) depended significantly on age, sex, LDL cholesterol, and HDL2 cholesterol, but not on HDL3 cholesterol or triglycerides.

CONCLUSIONS

In addition to LDL, HDL2, and HDL3 cholesterol, triglycerides also proved independently predictive of the extent of coronary atherosclerosis.
Upper limit of vulnerability reliably predicts the defibrillation threshold in humans.
Authors: Hwang C , Swerdlow C D , Kass R M , Gang E S , Mandel W J , Peter C T , Chen P S
Published: June 2012

BACKGROUND

The upper limit of vulnerability is the stimulus strength above which electrical stimulation cannot induce ventricular fibrillation even when the stimulus occurs during the vulnerable period of the cardiac cycle. The purpose of this study was to test the hypothesis that the upper limit of vulnerability can accurately predict the defibrillation threshold in patients undergoing implantable cardioverter-defibrillator (ICD) implantation using nonthoracotomy lead systems.

METHODS AND RESULTS

We studied 77 patients at the time of ICD implantation. Multiple endocardial-endocardial and endocardial-subcutaneous shock pathways were used. Two different protocols were used to test the upper limit of vulnerability. In protocol 1 (n = 17), the upper limit of vulnerability was tested with two shocks on the peak or the up-slope of the T wave of paced rhythm. The shocks were given randomly either at the peak and 20 milliseconds before the peak of T wave (n = 7) or at 20 and 40 milliseconds before the peak of T wave (n = 10). In protocol 2 (n = 60), the upper limit of vulnerability was tested with three shocks delivered at 0, 20, and 40 milliseconds before the peak of the T wave. The weakest shock that failed to induce ventricular fibrillation by a 5-J step-down or step-up method was defined as the upper limit of vulnerability. The defibrillation threshold was also determined by a 5-J step-down or step-up method. In protocol 1, the upper limit of vulnerability (9 +/- 6 J) was significantly lower than the defibrillation threshold (13 +/- 7 J) with a correlation coefficient of .87 and P < .001. In protocol 2, the upper limit of vulnerability (13 +/- 6 J) was not significantly different from the defibrillation threshold (13 +/- 6 J) with a correlation coefficient of .85 and P < .001. In 45 of the 60 patients, the upper limit of vulnerability was < or = 15 J; all had a defibrillation threshold of < or = 20 J. In 51 of the 60 patients, the upper limit of vulnerability was within 5 J of the defibrillation threshold. The upper limit of vulnerability overestimated the defibrillation threshold by > 10 J in 8 patients and underestimated the defibrillation threshold by > 10 J in only 1 patient. The overestimation and underestimation occurred only in patients with the upper limit of vulnerability > 15 J.

CONCLUSIONS

When tested with three shocks on and before the peak of the T wave, the upper limit of vulnerability accurately predicted the defibrillation threshold in patients undergoing ICD implantation using nonthoracotomy lead systems. This method required either one or no episodes of ventricular fibrillation in most patients.
Sudden death in the young. Is acute coronary thrombosis the major precipitating factor?
Authors: Corrado D , Basso C , Poletti A , Angelini A , Valente M , Thiene G
Published: June 2012

BACKGROUND

Atherosclerotic coronary artery disease, complicated by acute thrombosis, is the usual cause of sudden death in adults. This study addresses the pathology of coronary arteries in sudden death in the young (< or = 35 years old).

METHODS AND RESULTS

Among 200 consecutive cases of sudden death in youth in the Veneto region of Italy, 37 (33 men and 4 women, age 18 to 35 years; mean, 29.4 years) showed obstructive atherosclerotic coronary artery disease in the absence of other cardiac pathological conditions and causes of death. No patient had previous angina pectoris or myocardial infarction. Cardiac arrest occurred at rest in 30 subjects and was related to effort in 7. A histological study was carried out on the obstructive coronary plaques. Degree of lumen stenosis and extension of lipid core and intimal fibrocellular hyperplasia facing the lumen were calculated morphometrically. Immunohistochemistry and electron microscopy were used to further characterize the plaque cell population. Single-vessel disease was found in 33 patients and triple-vessel disease in 4, with an overall total of 45 obstructive plaques, 34 of which were located in the proximal left anterior descending coronary artery. At histological study, only 10 plaques from 10 patients showed acute thrombosis (occlusive in 5 and subocclusive in 5); the remaining 35 were uncomplicated. Thirty-one plaques were fibrous in nature, while the other 14 were atheromatous. Compared with the atheromatous lesions, the fibrous plaques were rarely complicated by thrombosis (3% versus 64%; P < .001) and distinctly exhibited a fairly well-preserved tunica media (81% versus 21%; P < .001) as well as a stratum of neointimal fibrocellular hyperplasia (68% versus 7%; P < .001), which on immunohistochemistry and electron microscopy appeared to be proliferating smooth muscle cells.

CONCLUSIONS

In our study population, sudden death was precipitated by acute coronary thrombosis in only 27% of patients with obstructive coronary atherosclerotic plaque. Most of the young victims of sudden death with obstructive coronary atherosclerosis showed single-vessel disease that affected the left anterior descending coronary artery and was due to fibrous plaques with neointimal smooth muscle cell hyperplasia and a preserved tunica media in the absence of acute thrombosis.
Oxygen uptake kinetics are determined by cardiac function at onset of exercise rather than peak exercise in patients with prior myocardial infarction.
Authors: Koike A , Hiroe M , Adachi H , Yajima T , Yamauchi Y , Nogami A , Ito H , Miyahara Y , Korenaga M , Marumo F
Published: June 2012

BACKGROUND

Resting cardiac function does not necessarily affect exercise capacity. However, to determine whether it affects early dynamics of oxygen uptake (VO2) during exercise, we measured VO2 during a constant work rate and during incremental exercise testing in patients with a history of myocardial infarction. VO2 kinetics and exercise capacity were compared between patients with relatively high left ventricular ejection fractions (LVEF > or = 35%, group 1) and those with lower ejection fractions (LVEF < 35%, group 2).

METHODS AND RESULTS

Forty patients with a history of prior myocardial infarction (age, 57 +/- 10 years) were monitored during 6 minutes of moderate constant work rate testing (40 +/- 8 W) and during symptom-limited incremental exercise testing with a cycle ergometer. VO2 was calculated from respired gas analysis on a breath-by-breath basis. Cardiac output determinations were made with a computerized cadmium telluride detector every 10 seconds during exercise. The VO2 time constant during constant work rate exercise was slower in group 2 (58.0 +/- 7.6 seconds) compared with group 1 (45.8 +/- 10.5 seconds, P = .0002), indicating slower kinetics in group 2. The time constant for the rise in cardiac output during exercise was also slower in patients with lower EFs (63.0 +/- 12.8 versus 50.0 +/- 12.2 seconds). However, there were no differences in exercise capacity parameters, such as the VO2 or cardiac output at peak exercise, obtained during incremental exercise testing among the two groups.

CONCLUSIONS

The prolonged time constant of VO2, which is primarily determined during early parts of exercise, reflects delayed cardiac output response in patients with severely impaired LV function. The time constant of VO2 during submaximal constant work rate exercise can be used as a sensitive and discriminant measure of impaired cardiac reserve in these patients.
Feasibility of serial intracoronary ultrasound imaging for assessment of progression of intimal proliferation in cardiac transplant recipients.
Authors: Pinto F J , Chenzbraun A , Botas J , Valantine H A , St Goar F G , Alderman E L , Oesterle S N , Schroeder J S , Popp R L
Published: June 2012

BACKGROUND

Serial quantitative coronary angiography is used to assess progression of coronary disease; however, pathology studies have demonstrated angiographic insensitivity for determining atheroma. Intracoronary ultrasound (ICUS) can define and measure the components of the arterial wall and offers the potential for precise quantitative assessment of disease progression on serial examinations. The present study was done to test the feasibility of serially assessing intimal proliferation at the same coronary site with ICUS imaging in cardiac transplant recipients.

METHODS AND RESULTS

ICUS imaging was done with a 30-MHz, 5F or 4.3F ultrasound imaging catheter at the time of angiography in 70 cardiac allografts (3.8 sites per patient) initially and 1 year later. Mean intimal thickness (IT), luminal area (LA), and total area (TA) of lumen plus intima and an index of intimal thickness (II = TA - LA/TA) were measured at each site. Additionally, vessels were graded using a scale incorporating criteria of intimal thickness and circumferential involvement. Side-by-side comparisons of paired angiograms were performed both to verify the similarity of ICUS imaging site and to detect new angiographic abnormalities. At least one site could be assessed serially by ICUS in 100% of patients, but only 189 of the original 263 coronary sites (72%) (2.7 sites per patient) could be matched satisfactorily on the second study. Thirty-nine patients (56%) had mild IT and 31 patients (44%) had moderate or severe IT on the initial study. Both groups showed the same IT progression the following year (delta = 0.05 +/- 0.13 versus 0.07 +/- 0.15 mm; P = NS). Twenty-seven of the 70 patients (39%) showed progression by ICUS. The 23 patients with ICUS progression and angiographically normal vessels had the same progression in intimal thickening as the 4 patients with ICUS progression but showing angiographic disease (delta = 0.17 +/- 0.13 versus 0.22 +/- 0.10 mm; P = NS).

CONCLUSIONS

Replication of the intracoronary imaging site by judgment of two observers at an initial study and at a second study 1 year later was possible in at least one vessel site in 100% of the 70 patients and in 72% (189 of 263) of the original imaging sites (2.7 sites per patient). Serial ICUS demonstrates progression of intimal thickening at specific sites in only some cardiac transplant patients. Progression of intimal proliferation can occur in individuals in the presence or absence of initially increased intimal thickening or of angiographic disease at the time of the initial studies. Angiography is insensitive for recognizing early intimal thickening of the coronary vessels.
Time course of coronary endothelial healing after injury due to ischemia and reperfusion.
Authors: Horwitz L D , Kaufman D , Keller M W , Kong Y
Published: June 2012

BACKGROUND

Although it has been demonstrated in short-term preparations that ischemia with early reperfusion results in coronary vascular injury manifested by abnormal endothelium-dependent relaxation and increased permeability to plasma proteins, it has not been clear whether these abnormalities are permanent or reversible.

METHODS AND RESULTS

In a canine model, regional coronary ischemia was accomplished by 1 hour of left anterior descending coronary artery ligation, and follow-up studies were performed after reperfusion for 1 hour, 48 hours, 2 weeks, or 9 weeks. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside. At 1 and 48 hours of reperfusion, relaxation of rings from the ischemic reperfused artery to ADP was blunted, but relaxation to nitroprusside was normal. At 2 weeks there was a nonsignificant trend toward a blunted response to ADP in the ischemic/reperfused rings, and at 9 weeks a completely normal response to ADP was observed. Coronary microvascular permeability was assessed by measurement of protein leak index (PLI), by using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. At 1 and 48 hours of reperfusion there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. There was a small increase in PLI at 2 weeks but a completely normal measurement at 9 weeks. Electron microscopy of ischemic/reperfused vessels demonstrated endothelial cell swelling and other abnormalities in epicardial arteries and the microcirculation at 48 hours of reperfusion but normal endothelium at 2 weeks of reperfusion.

CONCLUSIONS

After 1 hour of regional coronary ischemia, coronary endothelial injury occurs early in reperfusion with abnormalities in epicardial coronary artery endothelium-dependent relaxation, coronary microvascular permeability, and both epicardial coronary artery and microvascular histology. This pattern of injury persists for at least 48 hours, but there is partial functional and complete histological recovery within 2 weeks and complete functional recovery within 9 weeks.
Mithramycin inhibits myointimal proliferation after balloon injury of the rat carotid artery in vivo.
Authors: Chen S J , Chen Y F , Miller D M , Li H , Oparil S
Published: June 2012

BACKGROUND

Smooth muscle proliferation and extracellular matrix formation in the subintimal region of blood vessels that have been subjected to intimal injury are responsible for restenosis following balloon angioplasty of the coronary arteries and for accelerated atherosclerosis in a variety of other pathophysiological states. The immediate early-response gene c-myc is overexpressed in proliferating vascular smooth muscle cells in vitro, and c-myc antisense oligomers have been shown to reduce c-myc expression and to inhibit proliferation of vascular smooth muscle cells in culture. Mithramycin is a commercially available G-C-specific DNA binding drug that selectively inhibits transcription of genes, such as c-myc, that have G-C-rich promoter sequences. This study tested the hypothesis that mithramycin inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo.

METHODS AND RESULTS

Ten-week-old male Sprague-Dawley rats received mithramycin (150 micrograms/kg IP) or distilled H2O 1 hour before and 1 hour after balloon injury of the right common carotid artery. After 2 weeks, the rats were killed by overdose of pentobarbital, and the injured right and uninjured control left arteries were pressure-fixed and subjected to morphological analysis for evaluation of the degree of myointimal thickening. Separate groups of rats were killed at 2 and 6 hours after vascular injury, and total RNA from injured and control vessels of mithramycin- and vehicle-treated rats was subjected to Northern analysis for assessment of steady-state c-myc mRNA levels. The areas of neointima and the ratios of neointimal to medial area were significantly less in mithramycin-treated than in control rats (0.6 +/- 0.1 versus 1.2 +/- 0.1 mm2, P < .01 and 95 +/- 16% versus 190 +/- 14%, P < .01). Lumen size was significantly greater in mithramycin-treated than in control rats (1.5 +/- 0.1 versus 0.8 +/- 0.1 mm2, P < .01). Steady-state c-myc mRNA levels were increased 10-fold and 2-fold (compared with undamaged carotid arteries) at 2 and 6 hours after balloon injury, respectively; mithramycin treatment reduced c-myc mRNA levels at 2 and 6 hours by 66% and 53%, respectively.

CONCLUSIONS

These results support the hypothesis that systemic administration of mithramycin immediately (1 hour before and after intervention effectively inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo. Because mithramycin has been shown to be well tolerated by humans and to effectively inhibit transcription of c-myc in proliferating human cells, this agent may be useful in the prevention of coronary restenosis.
Local delivery of r-hirudin by a double-balloon perfusion catheter prevents mural thrombosis and minimizes platelet deposition after angioplasty.
Authors: Meyer B J , Fernández-Ortiz A , Mailhac A , Falk E , Badimon L , Michael A D , Chesebro J H , Fuster V , Badimon J J
Published: June 2012

BACKGROUND

The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis of the dilated lesion. Platelet-thrombus deposition occurs within minutes after injury, is primarily mediated by thrombin, causes acute occlusion, and contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested the hypothesis that high local concentrations of an antithrombin drug at the site of arterial injury following balloon angioplasty inhibit platelet thrombus formation equally or better than conventional systemic treatment and at lower systemic anticoagulant levels.

METHODS AND RESULTS

Balloon angioplasty of the carotid arteries of 29 pigs was performed using systemic intravenous treatment with heparin (100 U/kg, groups I and II), suboptimal r-hirudin (0.3 mg/kg, group III), and higher-dose r-hirudin (0.7 mg/kg, group IV), which is the lowest dose that completely inhibited arterial thrombosis in the pig. Immediately after balloon angioplasty of the first carotid, additional local therapy with placebo (group I) or r-hirudin (groups II, III, and IV; 0.3 mg/kg in 1 mL) was administered with distal perfusion through a new percutaneous double-balloon catheter. After 1 hour of local drug delivery, angioplasty of the contralateral carotid was performed. Reflow for 1 hour was permitted to both carotids to compare the short-term effect of local plus systemic treatment with systemic treatment on quantitative 111In-labeled platelet deposition and macroscopic mural thrombus formation on deeply injured carotid segments. Local drug delivery of placebo compared with systemic heparin treatment resulted in no change of platelet deposition (x 10(6)/cm2, mean +/- SEM) in controls (group I, 91.0 +/- 23.5 versus 80.8 +/- 19.4), but local delivery of r-hirudin resulted in a significant reduction in group II (15 +/- 2.5 versus 71.3 +/- 14.5; P < .02) and group III (11.4 +/- 2.5 versus 80.5 +/- 11.4; P < .01) and was borderline in group IV (7.4 +/- 1.8 versus 14.1 +/- 7.4; P = .05), respectively. The incidence of macroscopic mural thrombus formation with local and systemic treatment was 86% and 75% in group I, 16% and 70% in group II, 14% and 71% in group III, and 0% and 16% in group IV, respectively.

CONCLUSIONS

Local therapy with the specific thrombin inhibitor r-hirudin significantly reduces short-term quantitative platelet deposition and macroscopic mural thrombus formation following balloon angioplasty compared with systemic treatment of conventional doses of heparin and hirudin and requires a significantly smaller amount of the recombinant drug.
Angiotensinergic versus nonangiotensinergic hemodynamic effects of converting enzyme inhibition in patients with chronic heart failure. Assessment by acute renin and converting enzyme inhibition.
Authors: Kiowski W , Beermann J , Rickenbacher P , Haemmerli R , Thomas M , Burkart F , Meinertz T
Published: June 2012

BACKGROUND

The contribution of nonangiotensinergic effects of converting enzyme inhibitors to their hemodynamic effects in patients with chronic heart failure is not clear. A comparison of the effects of renin and converting enzyme inhibition should help to clarify this issue.

METHODS AND RESULTS

Thirty-six patients with chronic heart failure (New York Heart Association class II or III) were randomly assigned to receive double-blind either intravenous placebo, the renin inhibitor remikiren, or the converting enzyme inhibitor enalaprilat followed by coinfusion of a second placebo infusion, the addition of remikiren to enalaprilat, or the addition of enalaprilat to remikiren, respectively. Systemic hemodynamics (Swan-Ganz and radial artery catheters) were measured before (rest and submaximal recumbent bicycle ergometry), during (rest), and at the end (rest and exercise) of each 45-minute single- or combination-infusion period. Placebo did not change hemodynamics or renin activity. Effective inhibition of the renin-angiotensin system by remikiren and enalaprilat was indicated by increases of plasma immunoreactive renin together with rapid and complete inhibition of renin activity after remikiren and an increase after enalaprilat (all P < or = .05). Remikiren and enalaprilat rapidly and to a similar extent reduced resting blood pressure through a reduction of systemic vascular resistance, and these changes were significantly correlated to baseline plasma renin activity. Both compounds also decreased pulmonary artery, pulmonary capillary wedge, and right atrial pressures to a similar extent (P < .05). During exercise, pulmonary capillary wedge and right atrial pressures were equally reduced and stroke volume index was increased with remikiren and enalaprilat (P < .05) for both). The combination of converting enzyme with renin inhibition or vice versa did not cause additional hemodynamic changes.

CONCLUSIONS

Specific renin inhibition in patients with chronic heart failure produces short-term hemodynamic effects that are almost indistinguishable from those of converting enzyme inhibition. This finding and the lack of additional effects of converting enzyme inhibition added to renin inhibition suggest that nonangiotensinergic effects of converting enzyme inhibitors do not play a significant role in their short-term hemodynamic effects in patients with chronic heart failure.
Radiofrequency ablation of atrial flutter. Efficacy of an anatomically guided approach.
Authors: Kirkorian G , Moncada E , Chevalier P , Canu G , Claudel J P , Bellon C , Lyon L , Touboul P
Published: June 2012

BACKGROUND

Previous reports have shown that radiofrequency ablation can terminate atrial flutter and prevent recurrences. However, different methods have been used, and the current experience remains limited. The objective of the present study was to determine the efficacy of radiofrequency ablation of atrial tissue in patients with atrial flutter using an anatomically guided approach.

METHODS AND RESULTS

We treated 22 patients aged 30 to 73 years. Atrial flutter was recurrent for a mean of 5 years despite the administration of multiple antiarrhythmic drugs. Radiofrequency current was directed to the atrial isthmus between the inferior vena cava and the tricuspid ring, regardless of the morphology of local electrograms. Radiofrequency energy was applied during typical atrial flutter in 12 patients, atypical atrial flutter in 2 patients, and successively both forms in 8 patients. In 19 patients, atrial flutter abruptly terminated. In 3 patients, atrial flutter persisted despite 37, 48, and 25 applications, respectively. Atrial recordings demonstrated that atrial flutter termination occurred as a consequence of conduction block at the site of radiofrequency energy application, regardless of the type of atrial flutter. The number of applications before termination ranged from 1 to 82 (mean, 32). Atrial flutter could no longer be induced in every case. There were no complications. During a 13-month mean follow-up, atrial flutter recurred in only 2 of the 19 patients who had a successful ablation. Four patients experienced chronic atrial fibrillation, and 2 of them returned to sinus rhythm with antiarrhythmic therapy.

CONCLUSIONS

Radiofrequency ablation of atrial flutter using anatomic guidance is feasible and effective. Further experience is needed to delineate its role as an alternative approach to the management of refractory atrial flutter.
Feasibility of Exercise Stress Echocardiography for the Follow-up of Children With Coronary Involvement Secondary to Kawasaki Disease
Authors: Pahl Elfriede , Sehgal Rajesh , Chrystof Dale , Neches William H. , Webb Catherine L. , Duffy C. Elise , Shulman Stanford T. , Chaudhry Farooq A.
Published: June 2012

Background
The development of coronary aneurysms as sequelae of Kawasaki disease can result in myocardial ischemia, infarction, and sudden death. Traditionally, these patients have undergone coronary angiography and nuclear stress imaging for risk stratification and follow-up. However, angiography is invasive, and both modalities expose the patient to repeated radiation, which is an important issue in children. The purpose of this study was to determine the feasibility of performing exercise stress echocardiography in children diagnosed with coronary abnormalities secondary to Kawasaki disease.

Methods and Results
Treadmill exercise stress echocardiographic studies were performed in 28 children ages 6 to 16 years. All had acute Kawasaki disease 1 to 10 years before study, and coronary artery abnormalities were identified during previous echocardiographic imaging. Patients were exercised using a standard Bruce protocol. Transthoracic echocardiographic images, obtained in the parasternal long, short, apical two- and four-chamber views immediately before and after exercise, were digitized for review and analysis. In baseline studies before exercise, wall motion abnormalities were identified in 2 patients; these segments became normal with exercise. Two patients developed new exercise-induced wall motion abnormalities that corresponded to angiographically defined critical stenosis of the left anterior descending coronary artery. No patients had resting or exercise-induced ECG evidence of ischemia. There were no adverse reactions, and 26 of 28 patients had normal exercise tolerance.

Conclusions
Among patients with coronary artery involvement resulting from Kawasaki disease, exercise stress echocardiography is a safe, noninvasive procedure and may identify children with myocardial ischemia that was not detected with ECG stress test alone.
A Prospective Randomized Comparison in Humans of Biphasic Waveform 60-μF and 120-μF Capacitance Pulses Using A Unipolar Defibrillation System
Authors: Bardy Gust H. , Poole Jeanne E. , Kudenchuk Peter J. , Dolack G. Lee , Mehra Rahul , DeGroot Paul , Raitt Merritt H. , Jones Gregory K. , Johnson George
Published: June 2012

Background
Improving unipolar implantable cardioverter-defibrillator (ICD) effectiveness has favorable implications for ICD safety, efficacy, and size. Advances in defibrillation efficacy would accelerate ICD ease of use by decreasing device size and by minimizing morbidity and mortality related to an improved defibrillation safety margin. The specific purpose of the present study was to determine whether unipolar defibrillation efficacy could be improved further in humans by lowering biphasic waveform capacitance.

Methods and Results
We prospectively and randomly compared the defibrillation efficacy of a 60-μF and a 120-μF capacitance asymmetrical 65% tilt biphasic waveform using a unipolar defibrillation system in 38 consecutive cardiac arrest survivors before implantation of a presently available standard transvenous defibrillation system. The right ventricular defibrillation electrode had a 5-cm coil located on a 10.5F lead and was used as the anode. The system cathode was the electrically active 108-cm
2
surface area shell (or “can”) of a prototype titanium alloy pulse generator placed in a left infraclavicular pocket. The defibrillation pulse was derived from either a 60-μF or a 120-μF capacitance and was delivered from RV → CAN. Defibrillation threshold (DFT) stored energy, delivered energy, leading-edge voltage and current, pulse resistance, and pulse width were measured for both capacitances examined. The 60-μF capacitance biphasic pulse resulted in a stored-energy DFT of 8.5±4.1 J and a delivered-energy DFT of 8.4±4.0 J. In 34 of 38 patients (89%), the stored-energy DFT was <15 J. Leading-edge voltage at the DFT was 517±128 V. Mean pulse impedance for the 60-μF waveform was 60.6±7.1 Ω. The 120-μF capacitance biphasic pulse resulted in a stored-energy DFT of 10.1±7.4 J and a delivered-energy DFT of 10.0±7.2 J (
P
=.13 and .13, respectively). In 28 of 38 patients (74%), the stored-energy DFT was <15 J (
P
=.052). Leading-edge voltage at the DFT with the 120-μF capacitance pulse was 386±142 (
P
<.00001). Mean pulse impedance for the 120-μF waveform was 60.7±7.0 Ω (
P
=.80).

Conclusions
The results of the present study suggest that a relatively small capacitance, 60 μF, can be used for unipolar defibrillation systems without compromising defibrillation energy requirements compared with more typical ICD capacitance values, but this will require a higher circuit voltage. The use of lower capacitance also provides a modest increase in the percent of patients who have very low energy defibrillation requirements, an important issue should maximum ICD energy be decreased from the present level of 34 J. Such a move to smaller output devices could allow significant decreases in device size, a necessary feature of making cardioverter-defibrillator implantation comparable to that of standard pacemaker surgery.