bluuebunny/crossref_metadata_2025 huggingface dataset:
The Australian Schools Health and Fitness Survey. Physical fitness related to blood pressure but not lipoproteins.
Authors: Dwyer T , Gibbons L E
Published: June 2012

BACKGROUND

Recent research indicates that levels of conventional coronary heart disease risk factors in children are related to the premature development of atheroma. It is therefore important to determine how risk factors might be modified on a population scale in children.

METHODS AND RESULTS

In 1985, the Australian Schools Health and Fitness Survey was conducted on a representative sample of Australian schoolchildren aged 7 to 15 years. In children aged 9, 12, and 15, data on plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were obtained along with measurements of blood pressure, fitness, and body fatness. From an original sample of 2400 in these three age categories 1919 underwent the full set of measurements. Univariate analysis of these data revealed a strong association between body fatness and plasma lipids. There was no significant association between fitness (measured as physical work capacity at a heart rate of 170 beats per minute per kilogram of lean body mass) and plasma lipids, but a significant negative association was found for fitness and systolic blood pressure (r = -.12, P < .001). Multiple regression analysis revealed that the association of fitness with systolic blood pressure was only partly accounted for by the confounding effect of lower body fatness in fitter children.

CONCLUSIONS

These data collected on a representative sample of children under standardized conditions confirm a previous finding of a link between fitness and blood pressure in schoolchildren and also support a growing consensus that fitness is only weakly linked to plasma lipids and lipoproteins in children and adolescents.
Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.
Authors: Schwarz M , Katz S D , Demopoulos L , Hirsch H , Yuen J L , Jondeau G , LeJemtel T H
Published: June 2012

BACKGROUND

Since organic nitroesters and endothelium-derived nitric oxide mediate vasodilation through a final common pathway, that is, by activation of soluble guanylate cyclase in vascular smooth muscle, nitroglycerin (NTG) could specifically enhance the endothelium-dependent vasodilatory response to acetylcholine (Ach) in patients with congestive heart failure (CHF) and endothelial cell dysfunction. Accordingly, the net effects of an intra-arterial infusion of NTG (10(-9) mol/L) on endothelium-dependent and endothelium-independent vasodilation were assessed in the forearm circulation of patients with CHF.

METHODS AND RESULTS

The forearm blood flow responses to intra-arterial administration of graded concentrations of Ach (10(-7) to 10(-5) mol/L) were determined by venous occlusion plethysmography (mL/min per 100 mL) in 18 patients with CHF and 5 age-matched normal subjects before and during intra-arterial infusion of NTG (10(-9) mol/L) for 20 minutes. In eight patients, the duration of the infusion of NTG (n = 5) or vehicle control solution (n = 3) was extended to 12 hours with measurement of the forearm blood flow responses to Ach at 20 minutes, 4 hours, and 12 hours. In five additional patients, forearm blood flow response to intra-arterial administration of two doses of phentolamine (0.05 and 0.5 mg) were determined before and during a 20-minute NTG infusion. Regional administration of NTG 10(-9) mol/L did not change resting forearm blood flow in either normal subjects or patients with CHF. Before administration of NTG 10(-9) mol/L, intra-arterial infusions of Ach 10(-7), 10(-5) and 10(-5) mol/L increased forearm blood flow to 14.7 +/- 6.2, 20.2 +/- 4.7, and 38.4 +/- 7.9 mL/min per 100 mL in normal subjects and to 4.1 +/- 0.8, 5.0 +/- 1.1, and 10.6 +/- 2.3 mL/min per 100 mL in patients with CHF. After administration of NTG 10(-9) mol/L for 20 minutes, the vasodilatory response to Ach significantly increased to 5.6 +/- 1.0, 6.9 +/- 1.6, and 17.7 +/- 3.4 mL/min per 100 mL in patients with CHF but did not change in normal subjects. The enhanced forearm blood flow responses to administration of Ach observed after 20 minutes of NTG administration in patients with CHF were sustained throughout a 12-hour NTG infusion. In contrast, regional administration of NTG did not change the vasodilatory responses to phentolamine.

CONCLUSIONS

NTG, when administered intra-arterially for 20 minutes at a dose that does not affect resting forearm blood flow, specifically increased the vasodilatory response to intra-arterial administration of Ach in patients with CHF but not in normal subjects. The vasodilatory response to Ach was consistently enhanced by low-dose NTG throughout a 12-hour period. The vasodilating effects of organic nitroesters on the peripheral vasculature of patients with CHF may result in part from an interaction with the vascular endothelium.
Cardiovascular responses during static exercise. Studies in patients with complete heart block and dual chamber pacemakers.
Authors: Alexander T , Friedman D B , Levine B D , Pawelczyk J A , Mitchell J H
Published: June 2012

BACKGROUND

During static exercise in normal subjects, the mean arterial pressure increases as a result of an increase in heart rate and thereby cardiac output with no significant change in stroke volume or systemic vascular resistance. We hypothesized that if one component of the blood pressure response to static exercise, ie, heart rate, were fixed, plasticity of the neural control mechanisms during exercise would allow for preservation of the blood pressure response by alternative mechanisms.

METHODS AND RESULTS

Thirteen patients 20 to 68 years old with structurally normal hearts, complete heart block, and dual chamber pacemakers performed static exercise during three conditions: (1) normal dual chamber sensing and pacing mode, (2) heart rate fixed at the resting value obtained in the DDD mode of 78 +/- 4 beats per minute, and (3) heart rate fixed at the peak value obtained during exercise in the DDD mode of 94 +/- 4 beats per minute. Heart rate, blood pressure, and cardiac output were measured and stroke volume and systemic vascular resistance were calculated at rest and at 1 and 5 minutes during static one-leg extension at 20% of maximal voluntary contraction. The mean arterial pressures at rest and at 5 minutes were higher when the heart rate was fixed at the faster peak exercise heart rate. In the DDD mode, heart rate increased by 16 beats per minute and cardiac output by 1.1 L/min, with a resultant 25 mm Hg increase in mean arterial pressure at 5 minutes with no change in the stroke volume or systemic vascular resistance. In both fixed heart rate pacing modes, mean arterial pressure increased by 24 mm Hg when the heart rate was fixed at the resting heart rate and by 25 mm Hg when the heart rate was fixed at the faster peak exercise heart rate pacing modes associated with an increase in stroke volume, with similar increases in cardiac output. During static exercise there was no change in systemic vascular resistance from the resting value in any pacing mode.

CONCLUSIONS

When heart rate is fixed in the presence of normal left ventricular function, the mean arterial pressure increases normally during static exercise because of an increase in stroke volume with no change in the systemic vascular resistance.
Radiofrequency ablation therapy in idiopathic left ventricular tachycardia with no obvious structural heart disease.
Authors: Wen M S , Yeh S J , Wang C C , Lin F C , Chen I C , Wu D
Published: June 2012

BACKGROUND

The feasibility and efficacy of radiofrequency ablation therapy in idiopathic left ventricular tachycardia has not been assessed in a large group of patients.

METHODS AND RESULTS

Twenty consecutive patients with idiopathic left ventricular tachycardia and without structural heart disease underwent electrophysiological study, pharmacological interventions with administration of verapamil and adenosine, and radiofrequency ablation therapy. There were 17 men and 3 women with a mean age of 28 +/- 8 years. The QRS configuration during tachycardia was of right bundle branch block and superior axis in 13 patients, indeterminate axis in 6 patients, and right axis in 1 patient. The tachycardia was electrically inducible and responsive to verapamil but not to adenosine. Thirteen patients demonstrated entrainment. Activation and pace-mapping studies disclosed that the tachycardia originated from the inferior apical septum in 15 patients, the midseptum in 4 patients, and the anterior lateral wall of the left ventricle in 1 patient. Radiofrequency ablation was successful in 17 of the 20 patients (85%). The successful ablation sites were characterized by an endocardial activation time 30 milliseconds earlier than the onset of QRS during tachycardia and by a pace-mapping QRS similar to or closely resembling the tachycardia. All patients displayed sharp spikes preceding the local ventricular electrogram at the ablation site. However, these sharp spikes also were noted in 15 control patients and were not specific for this tachycardia; they persisted after ablation. There were no complications. A follow-up of 7 +/- 8 months in the 17 successfully ablated patients showed no symptomatic tachyarrhythmias without medications. Six patients underwent repeat electrophysiological study, and no induction of tachycardia was revealed.

CONCLUSIONS

Radiofrequency ablation therapy is effective and safe in patients with idiopathic left ventricular tachycardia. It should be considered as the primary therapeutic modality in these patients.
Left ventricular mass and subsequent blood pressure changes among middle-aged men in rural and urban Japanese populations.
Authors: Iso H , Kiyama M , Doi M , Nakanishi N , Kitamura A , Naito Y , Sato S , Iida M , Konishi M , Shimamoto T
Published: June 2012

BACKGROUND

It has been suggested that echocardiographically determined left ventricular mass (LVM) is useful in the prediction of hypertension. To examine the relation between LVM and subsequent blood pressure (BP) change, a 6- to 8-year follow-up was conducted in adult Japanese men.

METHODS AND RESULTS

LVM was determined by M-mode echocardiography using the American Society of Echocardiography formula among 354 normotensive men aged 30 to 59 years from a rural community (n = 193) and from urban companies (n = 161) in Japan between 1979 and 1983. BP was remeasured 6 to 8 years after baseline in 148 rural men (77%) and 127 urban men (79%). For men whose BP was remeasured, the mean +/- SD LVM index (LVM/body surface area [g/m2]) at baseline was 117 +/- 22 in rural men and 99 +/- 15 in urban men (the difference, P < .001). For both populations, LVM index was positively associated with age and physical activity but not with body mass index. Associations of LVM index with usual alcohol intake and initial BPs were generally weak. According to linear regression analyses after controlling for these covariates at baseline, a 20-g/m2 greater LVM index at baseline was associated with a 5 mm Hg increase in systolic and a 4 mm Hg increase in diastolic BP during the subsequent 6 to 8 years for urban men. A 1-mm greater average ventricular wall thickness was associated with a similar BP increase. For rural men, positive associations of LVM index with BP increase existed but were weak. The weaker association between LVM index and BP increase in rural compared with urban men was probably the result of effects of higher physical activity, leading to a larger left ventricular internal dimension. The increase in systolic and diastolic BPs over the 6 to 8 years of observation was significantly related to baseline LVM index in rural and urban men with a smaller internal dimension (rural men, < or = 49 mm; urban men, < or = 47 mm) but not in those with larger dimensions.

CONCLUSIONS

An increased LVM index predicts subsequent BP increase in middle-aged normotensive men in the presence of a normal or small internal dimension.
Biodegradable microspheres containing a colchicine analogue inhibit DNA synthesis in vascular smooth muscle cells.
Authors: March K L , Mohanraj S , Ho P P , Wilensky R L , Hathaway D R
Published: June 2012

BACKGROUND

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local application of agents capable of modulating vascular responses, including smooth muscle cell proliferation, has been achieved, but difficulty in maintaining active levels locally has been a factor limiting the efficacy of such approaches. One strategy to maintain adequate levels is the local delivery of microspheres that release active agents over sustained time periods.

METHODS AND RESULTS

We incorporated a colchicine analogue into biodegradable microspheres composed of a lactic acid/glycolic acid copolymer and characterized their drug release behavior as well as their effects on bovine aortic smooth muscle cells (BASMCs) in culture. Drug release was evaluated by spectrophotometric assay. Drug effects on DNA synthesis were measured by thymidine incorporation after addition of serum to subconfluent cells synchronized by serum withdrawal as well as in asynchronous cell populations. Polymeric microspheres incorporating 10% to 17% drug by weight and averaging 6 microns in size were found to release the colchicine analog in buffered saline solutions over more than several weeks. Drug-loaded particles inhibited DNA synthesis completely, with EC50 values ranging from 0.001 to 0.005 g% (wt/wt). Morphological changes suggesting microtubule depolymerization were observed after drug particle treatment, with similar EC50 values. Microspheres allowed to contact the cell surface demonstrated effects similar to those seen with microspheres suspended in the nutrient medium by porous polycarbonate filters, at EC50 values approximately fivefold lower. In contrast, control microspheres composed only of polymer with no incorporated active drug demonstrated no observable toxicity to BASMCs and < 40% inhibition of thymidine incorporation even in suspensions containing up to 0.5 g% particles.

CONCLUSIONS

Biodegradable microspheres were fashioned that release a colchicine analogue and inhibit DNA synthesis in smooth muscle cells. Drug-loaded polymeric particles are candidates for local delivery at sites of arterial injury to decrease restenosis.
Relation between coronary artery stenosis assessed by visual, caliper, and computer methods and exercise capacity in patients with single-vessel coronary artery disease. The Veterans Affairs ACME Investigators.
Authors: Folland E D , Vogel R A , Hartigan P , Bates E R , Beauman G J , Fortin T , Boucher C , Parisi A F
Published: June 2012

BACKGROUND

Practitioners often assume a close relation between angiographic coronary artery stenosis and patient functional capacity. To test this unproven hypothesis, we analyzed the relation between coronary artery stenosis measured by different methods and maximal treadmill exercise tolerance in patients with single-vessel disease before and after intervention by percutaneous transluminal coronary angioplasty (PTCA).

METHODS AND RESULTS

Coronary angiography and maximal exercise testing off anti-ischemic medication were performed before random assignment of 227 patients with single-vessel coronary artery disease to PTCA or drug therapy. Six months later, angiography and exercise testing were repeated with patients assigned to PTCA off anti-ischemic therapy so that the altered coronary stenosis was the only consistent variable. Patients assigned to drug therapy were exercised on drug therapy. Coronary stenosis was assessed visually by the local investigator and quantitatively by blinded caliper and computer methods in central laboratories. Variabilities of caliper and computer measurements were established in a subset read twice. Visually estimated stenosis > or = 90% at baseline was associated with shorter exercise duration (7.9 versus 9.2 minutes, P < .04). Similar segregation at baseline was not observed with caliper or computer methods. Regardless of the method of measurement used, correlation between changes of lesion severity and exercise duration from baseline to follow-up was poor. Patients were angiographically classified as "better," "unchanged," or "worse" if follow-up stenosis was below, within, or above 2 SD of mean technical variability from baseline (+/- 18.8%, caliper, +/- 14.6%, computer). Exercise duration for PTCA patients improved among those with better lesions (+2.4 minutes, n = 50, P = .001) but also among those with unchanged lesions (+1.9 minutes, n = 41, P < or = .001). Unchanged medically treated patients improved less (+0.5 minutes, n = 86, P = .04). Results were similar when patients were angiographically classified by minimum lumen diameter.

CONCLUSIONS

Handheld calipers and quantitative coronary angiography are equivalent techniques for making anatomic measurements. Neither method identified patients having reduced exercise capacity at baseline as well as visual estimation. The relation between changes of coronary stenosis and exercise duration is highly variable, at least in part because of the insensitivity of angiographic methods for detecting small but potentially important changes. Minimal anatomic improvement 6 months after PTCA does not preclude a good functional outcome. Contrary to common belief, angiographic stenosis does not correlate well with functional capacity, even in patients with single-vessel disease.
Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by 111In monoclonal antimyosin antibodies.
Authors: Obrador D , Ballester M , Carrió I , Moya C , Bosch I , Martí V , Bernà L , Estorch M , Udina C , Marrugat J
Published: June 2012

BACKGROUND

The clinical relevance of myocardial cell damage in dilated cardiomyopathy is uncertain. Myocardial uptake of 111In monoclonal antimyosin antibodies (MAA) was used to study myocardial damage in patients with idiopathic (IDC) and alcoholic (ADC) dilated cardiomyopathy and to assess its prognostic implications.

METHODS AND RESULTS

MAA and echocardiographic studies were performed in 117 patients. Intensity of antibody uptake was measured by heart-to-lung ratio (HLR) (normal < 1.55). Studies were repeated in survivors and patients who did not receive a cardiac transplant. Follow-up extended up to 62 months (mean, 23 +/- 16 months). Eighty-eight patients with IDC showed a 77% prevalence of abnormal MAA. After acute-onset IDC, reduction of HLR (1.81 +/- 0.2 to 1.56 +/- 0.1) (P = .007) with improvement in ejection fraction (EF) (35 +/- 10% to 46 +/- 14%) (P = .018) was observed. No changes in HLR or EF were detected in patients with chronic stable IDC. Twenty-nine patients with ADC showed a lower prevalence (48%) of abnormal MAA studies than those with IDC (P = .003). HLR was higher in 13 active (1.78 +/- 0.3) than in 16 past consumers (1.49 +/- 0.2) (P = .019); in the former, HLR decreased to 1.44 +/- 0.2 (P = .012), and EF improved (35 +/- 14% to 53 +/- 18%) (P = .05) after abstention. Intensities of uptake HLR of > 1.87 were associated with increased risk of death or transplantation.

CONCLUSIONS

In patients with IDC, variations of MAA uptake are detected in patients who present acutely but not in those with chronic stable disease. In patients with ADC, MAA uptake mainly depends on alcohol consumption. In both situations, reduction of uptake correlates with improvement of ventricular function. Higher intensities of MAA uptake are associated with a worse outcome. The intensity of antibody uptake, along with other clinical and functional variables, may be helpful in risk stratification of patients with dilated cardiomyopathy.
Mechanisms of entrainment of human common flutter studied with multiple endocardial recordings.
Authors: Cosío F G , López Gil M , Arribas F , Palacios J , Goicolea A , Núñez A
Published: June 2012

BACKGROUND

The mechanisms of common atrial flutter entrainment have not been directly studied in humans.

METHODS AND RESULTS

Endocardial mapping in six cases of common flutter showed large right atrial (RA) reentry circuits. Activation was craniocaudal in the anterolateral right atrium and caudocranial in the septum. The inferior vena cava-tricuspid isthmus (IVC-TV) closed the circuit. The high right atrium was paced at progressively shorter cycle lengths (CLs) in all, and the IVC-TV was paced in three cases. We recorded six to eight simultaneous RA electrograms from septum and anterior wall. Transient entrainment was recognized from all sites by capture of all electrograms at two or more paced CLs, with total or partial preservation of baseline flutter sequence and return to baseline after pacing. Antidromic circuit penetration was documented in five cases during high RA pacing and in one with IVC-TV pacing. Short CLs induced orthodromic conduction delays that resulted in a postpacing pause longer than basal flutter CL. ECG fusion with high RA pacing correlated poorly with antidromic septal penetration. This was related to overlap of orthodromic septal activation with anterior wall activation of the following cycle. Pacing disorganized flutter into a brief irregular rapid rhythm in two cases and atrial fibrillation in one case. In two cases, complete antidromic septal penetration led to sudden flutter interruption, and in another case it led to circuit inversion.

CONCLUSIONS

Direct recordings confirm orthodromic and antidromic penetration of flutter circuits by high and low RA pacing. Short CLs modify the circuit. Disorganization is the most common mode of flutter interruption.
T-cell receptor V beta gene expression in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3.
Authors: Seko Y , Yagita H , Okumura K , Yazaki Y
Published: June 2012

BACKGROUND

In viral myocarditis, we previously reported that natural killer cells infiltrate the heart first, then activated T cells infiltrate second and play an important role in the pathogenesis of the myocardial damage.

METHODS AND RESULTS

To elucidate the nature of T-cell infiltration, using a murine model of acute myocarditis caused by coxsackievirus B3, we analyzed the expression of T-cell receptor (TCR) V beta genes in infiltrating cells in the heart by polymerase chain reaction (PCR). The PCR-amplified products were confirmed by Southern blot hybridization with a C beta cDNA probe. In contrast to spleen lymphocytes, the repertoire of V beta gene transcripts in the heart was restricted. The infiltrating cells expressing V beta 10 were found in six of eight hearts of mice with acute myocarditis. The infiltrating cells expressing V beta 8 and V beta 13 were found in four of eight hearts with myocarditis, respectively. Immunoperoxidase staining of serial sections of the heart of myocarditis for TCR alpha beta chains and TCR V beta 10 confirmed that the dominant population of infiltrating T cells expressed V beta 10 gene products.

CONCLUSIONS

The restricted usage of TCR genes by infiltrating T-cells may indicate that a specific antigen in heart with myocarditis is targeted. Our findings raise the possibility of immunotherapy with monoclonal antibodies specific for TCR V beta elements to prevent T-cell-mediated myocardial damage in viral myocarditis.
Effect of ischemic preconditioning on interstitial purine metabolite and lactate accumulation during myocardial ischemia.
Authors: Van Wylen D G
Published: June 2012

The purpose of this study was to determine the effect of ischemic preconditioning on the changes in interstitial fluid (ISF) purine metabolites and lactate during prolonged regional myocardial ischemia. The study consisted of two groups of anesthetized dogs: a control group (n = 13) that was exposed to 60 minutes of regional myocardial ischemia and a preconditioned group (n = 10). In the preconditioned group, regional myocardial ischemia was induced for two 5-minute episodes, each followed by 10 minutes of reperfusion. These preconditioning episodes were followed by 60 minutes of sustained regional ischemia. Cardiac ISF was sampled by microdialysis probes implanted in the left ventricular myocardium; dialysate levels served as indices of ISF concentrations. In the preconditioned group, dialysate concentrations of adenosine, inosine, hypoxanthine, total purines, and lactate increased during each of the 5-minute ischemia episodes, with further increases occurring during the first 5 minutes of reperfusion. However, the increases in dialysate purine metabolites during the first period of ischemia/reperfusion were greater than those that occurred during the second ischemia/reperfusion. In addition, preconditioning reduced the rate of ISF purine metabolite and lactate accumulation during the prolonged ischemia when compared with nonpreconditioned animals. These data suggest that preconditioning reduces the energy imbalance that occurs during subsequent myocardial ischemia and thereby diminishes the rate of net adenine nucleotide degradation and cellular production and release of purine metabolites and lactate. In addition, the increase in ISF adenosine seen during the preconditioning episode is consistent with the notion that preconditioning-induced cardioprotection is mediated in part by the action of adenosine at extracellular A1 adenosine receptors.
Enhancement of regional myocardial efficiency and persistence of perfusion, oxidative, and functional reserve with paired pacing of stunned myocardium.
Authors: Bergmann S R , Weinheimer C J , Brown M A , Perez J E
Published: June 2012

BACKGROUND

Stunned myocardium reflects postreperfusion dysfunction in myocardium that is destined to ultimately fully recover. Most investigators attribute postreperfusion stunning to a primary defect in excitation-contraction coupling or to an altered sensitivity of the myofilaments to calcium. The aim of the present study was to evaluate the interrelation between myocardial perfusion, oxidative metabolism, and function in an effort to better characterize the phenomenon of myocardial stunning, to define the regional efficiency of stunned myocardium, and to characterize its reserve capacity.

METHODS AND RESULTS

Regional myocardial perfusion (measured with radiolabeled microspheres), myocardial oxygen consumption (MVO2) (quantified with positron emission tomography using 1-11C-acetate), and myocardial function (assessed with two-dimensional echocardiography) were evaluated in 12 anesthetized, closed-chest dogs subjected to 15 minutes of left anterior descending coronary artery occlusion followed by reperfusion. To evaluate flow, oxidative, and functional reserve after measurements were obtained 1 hour after reperfusion, dogs were subjected to paired pacing (an inotropic stimulus that does not alter systemic hemodynamics), and measurements were repeated. One hour after reperfusion, stunned myocardium was characterized by near-normal levels of myocardial perfusion (0.57 +/- 0.13 mL/g per minute, 81 +/- 13% of that in remote, normal regions) but severe dyskinesis (echo score, 2.6 +/- 0.7; percent wall thickening, 14 +/- 20%). Despite the low level of contractile function, MVO2 averaged 1.72 +/- 0.7 mumol/g per minute, 71 +/- 27% of that observed in remote myocardium. Regional myocardial efficiency (systolic wall thickening divided by MVO2) was markedly diminished. With paired pacing, myocardial perfusion increased proportional to that in remote myocardium, systolic function improved (echo score, 1.4 +/- 0.7; percent wall thickening, 30 +/- 15%), and regional MVO2 nearly doubled (to 3.41 +/- 1.82 mumol/g per minute, P < .05 for each paired measurement). Importantly, with paired pacing, regional myocardial efficiency nearly normalized in reperfused myocardium.

CONCLUSIONS

Stunned myocardium is characterized by near-normal levels of perfusion and oxygen consumption despite marked dyskinesis. Myocardial efficiency is poor. With inotropic stimulation (in the present study, paired pacing), reperfused myocardium demonstrated considerable perfusion, oxidative, and functional reserve and a dramatic improvement in myocardial efficiency. These results may have implications for the treatment of postreperfusion pump failure.
Incidence and treatment of 'no-reflow' after percutaneous coronary intervention.
Authors: Piana R N , Paik G Y , Moscucci M , Cohen D J , Gibson C M , Kugelmass A D , Carrozza J P , Kuntz R E , Baim D S
Published: June 2012

BACKGROUND

Profound reduction in antegrade epicardial coronary flow with concomitant ischemia is seen occasionally during percutaneous coronary intervention despite the absence of evident vessel dissection, obstruction, or distal vessel embolic cutoff. In a prior small series of cases, this "no-reflow" phenomenon appeared to be promptly reversed by the intra-coronary administration of verapamil.

METHODS AND RESULTS

To further understand the prevalence of this syndrome and its responsiveness to the proposed therapy, we reviewed 1919 percutaneous interventions performed between January 1991 and April 1993. During the study period, 39 patients (2.0%) met our criteria for no reflow, 37 of whom were treated with intracoronary nitroglycerin followed by intracoronary verapamil and 2 of whom received intracoronary nitroglycerin alone. An additional 16 patients (0.8%) were given verapamil as part of the management of a flow-limiting dissection or distal embolus (mechanical obstruction). Intracoronary verapamil (50 to 900 micrograms, total dose) improved TIMI flow grade in 89% of no-reflow patients and markedly reduced the number of cineframes between contrast injection and opacification of a selected distal landmark (from 91 +/- 56 to 38 +/- 21 frames, P < .001). By contrast, only 19% of patients with epicardial mechanical obstruction showed improvement in TIMI flow grade after verapamil, with minimal reduction in frames to opacification (from 107 +/- 42 to 101 +/- 69, P = .73).

CONCLUSIONS

The no-reflow phenomenon--reduction in distal flow without apparent dissection or distal embolization--occurs in 2% of coronary interventions. It generally responds promptly to intracoronary verapamil administration, suggesting that distal microvascular spasm may be its etiology.
Intracoronary angiotensin-converting enzyme inhibition improves diastolic function in patients with hypertensive left ventricular hypertrophy.
Authors: Haber H L , Powers E R , Gimple L W , Wu C C , Subbiah K , Johnson W H , Feldman M D
Published: June 2012

BACKGROUND

There is increasing recognition of myocardial angiotensin-converting enzyme, which is induced with the development of left ventricular hypertrophy (LVH). The potential physiological significance of subsequent increased angiotensin I to II conversion in the presence of LVH is unclear but has been postulated to cause abnormal Ca2+ handling and secondary diastolic dysfunction. Accordingly, we hypothesized that acute angiotensin-converting enzyme inhibition would result in decreased production of angiotensin II and improved active (Ca(2+)-dependent) relaxation in patients with hypertensive LVH.

METHODS AND RESULTS

Intracoronary (IC) enalaprilat was administered to 25 patients with and without LVH secondary to essential hypertension. Indexes of diastolic and systolic LV function were determined from pressure (micromanometer)-volume (conductance) analysis at steady state and with occlusion of the inferior vena cava. Patients were divided into those receiving high- (5.0 mg, n = 15) and low-dose (1.5 mg, n = 10) IC enalaprilat during a 30-minute infusion at 1 mL/min. The high-dose patients were further divided along the median normalized LV wall thickness of 0.671 cm/m2. The time constant of isovolumic relaxation (TauL) was prolonged at baseline in patients receiving high-dose enalaprilat with wall thickness > 0.671 cm/m2 (TauL, 56 +/- 2 versus 44 +/- 2 and 45 +/- 2 milliseconds, respectively, P < .01 by ANOVA) and shortened only in this patient group (TauL, 49 +/- 3 versus 46 +/- 2 and 43 +/- 2 milliseconds, respectively, P < .01 versus baseline and other groups by ANOVA). The improvement in TauL was directly proportional to the degree of LVH (r = .92, P < .001). Although there was a decrease in LV end-diastolic pressure (23 +/- 2 to 15 +/- 1 mm Hg, P < .01) and volume (86 +/- 8 to 67 +/- 9 mL/m2, P < .05) in those patients with a reduction in TauL, this is due to movement down a similar diastolic pressure-volume relation with no change in chamber elastic stiffness (0.023 +/- 0.002 to 0.025 +/- 0.004 mL-1, P = NS).

CONCLUSIONS

Intracoronary enalaprilat resulted in an improvement in active (Ca(2+)-dependent) relaxation in those patients with more severe hypertensive LVH. The improvement in active relaxation was directly proportional to the severity of LVH. These results support the hypothesis that the cardiac renin-angiotensin system is an important determinant of active diastolic function in hypertensive LVH.
Effects of converting enzyme inhibition on heart period variability in patients with acute myocardial infarction.
Authors: Bonaduce D , Marciano F , Petretta M , Migaux M L , Morgano G , Bianchi V , Salemme L , Valva G , Condorelli M
Published: June 2012

BACKGROUND

Heart period variability provides useful prognostic information on autonomic cardiac control, and a strong association has been demonstrated after myocardial infarction (MI) between cardiac mortality, sudden death, and reduced total power, ultralow-frequency (ULF) power, and very-low-frequency (VLF) power. Converting enzyme inhibitors are widely used in MI patients, but their influence on heart period variability remains to be defined.

METHODS AND RESULTS

Time- and frequency-domain measures of heart period variability were calculated from 24-hour Holter monitoring in 40 patients with a first uncomplicated MI. After baseline examination between 48 and 72 hours after symptom onset, patients were randomly assigned to placebo or captopril administration, and on the third day, 24-hour Holter monitoring was repeated. No changes in time and frequency domain were detectable after placebo. After captopril, the SD of all normal RR (NN) intervals (SDNN) increased from 90 +/- 29 to 105 +/- 30 milliseconds (P < .01); the SD of the average NN intervals for all 5-minute segments (SDANN index) and the mean of the SDs of all NN intervals for all 5-minute segments (SDNN index) also increased from 74 +/- 24 to 90 +/- 26 milliseconds (P < .01) and from 45 +/- 17 to 49 +/- 15 milliseconds (P < .05), respectively. The root mean square successive difference (r-MSSD) and the percent of differences between adjacent NN intervals > 50 milliseconds (pNN50) remained unchanged. In regard to frequency-domain measures, after captopril, total power (ln unit) increased from 8.28 +/- 0.42 to 8.47 +/- 0.30 (P < .01); considering the frequency bands, a significant increase was observed in ULF (P < .01), VLF (P < .05), and low-frequency (LF) power (P < .05), whereas high-frequency (HF) power remained unchanged.

CONCLUSIONS

This study supports the hypothesis that the renin-angiotensin system modulates the amplitude of ULF and VLF power. Furthermore, it demonstrates that in MI patients, converting enzyme inhibition favorably modifies measures of heart period variability strongly associated with a poor prognosis.
Magnetic resonance imaging during dobutamine stress for detection and localization of coronary artery disease. Quantitative wall motion analysis using a modification of the centerline method.
Authors: van Rugge F P , van der Wall E E , Spanjersberg S J , de Roos A , Matheijssen N A , Zwinderman A H , van Dijkman P R , Reiber J H , Bruschke A V
Published: June 2012

BACKGROUND

Quantitative measurement of wall motion is essential to assess objectively the functional significance of coronary artery disease. We developed a quantitative wall thickening analysis on stress magnetic resonance images. This study was designed to assess the clinical value of magnetic resonance imaging (MRI) during dobutamine stress for detection and localization of myocardial ischemia in patients with suspected coronary artery disease.

METHODS AND RESULTS

Thirty-nine consecutive patients with clinically suspected coronary artery disease referred for coronary arteriography and 10 normal volunteers underwent gradient-echo MRI at rest and during peak dobutamine stress (infusion rate, 20 micrograms.kg-1.min-1). MRI was performed in the short-axis plane at four adjacent levels. Display in a cine loop provided a qualitative impression of regional wall motion (cine MRI). A modification of the centerline method was applied for quantitative wall motion analysis by means of calculation of percent systolic wall thickening. Short-axis cine MRI images were analyzed at 100 equally spaced chords constructed perpendicular to a centerline drawn midway between the end-diastolic and end-systolic contours. Dobutamine MRI was considered positive for coronary artery disease if the percent systolic wall thickening of more than four adjacent chords was < 2 SD below the mean values obtained from the normal volunteers. The overall sensitivity of dobutamine MRI for the detection of significant coronary artery disease (diameter stenosis > or = 50%) was 91% (30 of 33), specificity was 80% (5 of 6), and accuracy was 90% (35 of 39). The sensitivity for identifying one-vessel disease was 88% (15 of 17), for two-vessel disease 91% (10 of 11), and for three-vessel disease 100% (5 of 5). The sensitivity for detection of individual coronary artery lesions was 75% for the left anterior descending coronary artery, 87% for the right coronary artery, and 63% for the left circumflex coronary artery.

CONCLUSIONS

Dobutamine MRI clearly identifies wall motion abnormalities by quantitative analysis using a modification of the centerline method. Dobutamine MRI is an accurate method for detection and localization of myocardial ischemia and may emerge as a new noninvasive approach for evaluation of patients with known or suspected coronary artery disease.
Improvement of the age-related impairment in left ventricular diastolic filling with verapamil in the normal human heart.
Authors: Arrighi J A , Dilsizian V , Perrone-Filardi P , Diodati J G , Bacharach S L , Bonow R O
Published: June 2012

BACKGROUND

Left ventricular (LV) diastolic function declines with the normal aging process. Because these changes are related to impaired active LV relaxation as well as to structural alterations, we hypothesized that verapamil might improve LV filling in elderly normal subjects compared with young normal subjects.

METHODS AND RESULTS

We studied 27 normal volunteers (between 20 and 71 years old), with normal exercise tests and echocardiograms, by radionuclide angiography before and after 3 to 4 days of oral verapamil therapy. Indexes of global LV function were derived from analysis of background-corrected time-activity curves. Subjects were recruited from three age groups: young (26 +/- 4 years, n = 10), middle-aged (46 +/- 5 years, n = 9), and elderly (66 +/- 3 years, n = 8). Baseline resting heart rate, blood pressure, peak systolic wall stress, and LV ejection fraction did not differ among groups. Baseline peak LV filling rate (expressed in fractional stroke volume per second) was reduced in the middle-aged group (5.8 +/- 1.2, P < .01) and the elderly group (4.3 +/- 1.0, P < .01) compared with the young group (7.8 +/- 1.2). With verapamil, resting heart rate, peak systolic wall stress, LV ejection fraction, and peak ejection rate did not change in any group. Peak filling rate increased in the middle-aged group (to 6.8 +/- 1.5 SV/s, P < .01) and the elderly group (to 5.7 +/- 1.0 SV/s, P < .01) but did not change in the young group (8.0 +/- 1.4 SV/s). Also, time to peak filling rate decreased with verapamil in the elderly group (from 185 +/- 31 to 147 +/- 15 milliseconds, P < .01). The magnitude of change in filling rate was correlated positively with age (r = .55, P < .005).

CONCLUSION

Verapamil selectively enhances LV diastolic filling in middle-aged and elderly subjects, compared with young adults, without affecting systolic function. This observation supports the hypothesis that the impairment of LV filling accompanying the normal aging process is, at least in part, a reversible phenomenon.
Radiofrequency catheter ablation of atriofascicular and nodoventricular Mahaim tracts.
Authors: Grogin H R , Lee R J , Kwasman M , Epstein L M , Schamp D J , Lesh M D , Scheinman M M
Published: June 2012

BACKGROUND

Several mechanisms have been proposed to explain the pathogenesis of tachycardia in patients with Mahaim tracts. The tachycardia may involve antegrade conduction over an atriofascicular pathway with decremental properties or a nodofascicular pathway.

METHODS AND RESULTS

We report six patients with recurrent episodes of preexcited tachycardia with findings consistent with "Mahaim tract" conduction. All patients exhibited decremental antegrade preexcited conduction with atrial pacing and a preexcited tachycardia with initial activation of the proximal right bundle branch. In four patients (group 1), atrial premature complexes (APCs) induced at the tricuspid annulus just after the inscription of the septal atrial electrogram and during left bundle branch block preexcited tachycardia advanced the next preexcited ventricular complex. In these patients, discrete Mahaim potentials were inscribed over the right anterolateral or lateral tricuspid annulus. Two patients (group 2) had evidence of dual atrioventricular nodal conduction. APCs during left bundle branch block tachycardia just after inscription of the septal atrial electrogram failed to advance the next ventricular complex with similar preexcited morphology, and no Mahaim potentials could be recorded from the tricuspid annulus. In group 1 patients, application of radiofrequency energy to sites recording the Mahaim potentials resulted in tachycardia cure. For patients in group 2, selective slow atrioventricular nodal pathway ablation in the midseptal region resulted in complete ablation of both the slow atrioventricular nodal pathway and Mahaim conduction in two patients.

CONCLUSIONS

Mahaim tachycardia can be due to atriofascicular pathways, which may be ablated over the right tricuspid annulus, or to septal pathways, which may arise from the slow atrioventricular nodal pathway in patients with dual atrioventricular nodal physiology. In the latter circumstance, successful ablation is achieved by placing the lesion in the midseptal region.
Myocardial release of malondialdehyde and purine compounds during coronary bypass surgery.
Authors: Lazzarino G , Raatikainen P , Nuutinen M , Nissinen J , Tavazzi B , Di Pierro D , Giardina B , Peuhkurinen K
Published: June 2012

BACKGROUND

Free radicals and lipid peroxidation have been suggested to play an important role in the pathophysiology of myocardial reperfusion injury. The purpose of the present study was to monitor myocardial malondialdehyde (MDA) production as an index of lipid peroxidation during ischemia-reperfusion sequences in patients undergoing elective coronary bypass grafting. There has been a lot of debate on the role of xanthine oxidase as a potential superoxide anion generator and thus lipid peroxidation in human myocardium. To evaluate the activity of xanthine oxidase pathway, we measured the changes in the transcardiac concentration differences in adenosine, inosine, hypoxanthine, xanthine, and uric acid.

METHODS AND RESULTS

The coronary sinus-aortic root differences (CS-Ao) of MDA, oxypurines, and nucleosides were measured by a recently developed ion-pairing high-performance liquid chromatographic (HPLC) method. Fifteen patients were included in the study, and 13 of them demonstrated a more than 10-fold increase in net myocardial production of MDA on intermittent reperfusion during the aortic cross-clamp period. In 2 patients, MDA was not detectable in any of the CS or Ao samples. Before aortic cross-clamping, the CS-Ao concentration differences in adenosine, inosine, hypoxanthine, xanthine, and uric acid were 0.59 +/- 0.19, 0.23 +/- 0.05, 0.89 +/- 0.36, 0.58 +/- 0.32, and 11.4 +/- 4.9 mumol/L, respectively. After aortic cross-clamping, the sum of the transcardiac differences of these compounds increased up to 2.8-fold and then gradually decreased after declamping of the aorta. There was a weak positive correlation between transcardiac concentration differences of MDA and xanthine plus uric acid (r = .48, P < .01). The postoperative functional recovery or leakage of cardiac enzymes was not affected by the level of MDA net release during the aortic cross-clamp period, however.

CONCLUSIONS

We conclude that myocardial lipid peroxidation, estimated as MDA formation, is common during intermittent ischemia-reperfusion sequences in coronary bypass surgery, although some patients may be better protected. Xanthine oxidase appears to be operative in human myocardium, and free radicals generated in this reaction might also be involved in the observed lipid peroxidation process. Increased degradation of myocardial adenine nucleotides and concomitant lipid peroxidation may play a specific role in the development of reperfusion injury. In this study, however, more extensive lipid peroxidation was not associated with impaired functional recovery.
Coronary thrombolysis with Desmodus salivary plasminogen activator in dogs. Fast and persistent recanalization by intravenous bolus administration.
Authors: Witt W , Maass B , Baldus B , Hildebrand M , Donner P , Schleuning W D
Published: June 2012

BACKGROUND

DSPA (Desmodus salivary plasminogen activator) is a new thrombolytic agent corresponding to a natural plasminogen activator discovered in the saliva of the vampire bat Desmodus rotundus. Compared with tissue plasminogen activator (TPA), DSPA, produced in a recombinant cell line, is more fibrin cofactor dependent than TPA.

METHODS AND RESULTS

The thrombolytic properties of DSPA and TPA were compared in a canine model of copper coil-induced coronary thrombosis. All dogs received heparin 200 IU/kg IV and SC. Whereas controls did not reperfuse within 180 minutes (none of six), intravenous bolus administration of DSPA at 25, 50, and 100 micrograms/kg resulted in a 100% incidence (6 of 6) of recanalization within 37, 23, and 18 minutes, respectively. TPA at 63 and 125 micrograms/kg reopened the coronaries in 33% (two of six) and 50% (three of six) of cases within 40 minutes. Eighty-three percent (5 of 6) of the arteries were still patent 3 hours after 50 and 100 micrograms/kg DSPA, whereas only 20% (one of five) of all coronaries originally recanalized with both doses of TPA were still open at 3 hours. Plasma levels of alpha 2-antiplasmin decreased significantly only with 125 micrograms/kg TPA. The clearance of DSPA (2.3 to 3.5 mL.min-1.kg-1) was lower compared with TPA (11.4 to 20 mL.min-1.kg-1) due to a prolonged terminal half-life.

CONCLUSIONS

In a canine coronary thrombosis model, DSPA exhibited higher potency and recanalized coronary arteries faster and with a lower incidence of reocclusion than TPA. Its properties may translate into a higher efficacy in patients compared with available thrombolytic agents. The long half-life of DSPA may allow for single bolus administration in the treatment of acute myocardial infarction.