bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Doppler assessment of valvular regurgitation.
Authors: Enriquez-Sarano M , Bailey K R , Seward J B , Tajik A J , Krohn M J , Mays J M
Published: June 2012

BACKGROUND

Quantitation of valvular regurgitation remains a challenge. The accuracy of quantitative Doppler is controversial, and its ability to measure regurgitant volume is unknown; therefore, it is not widely used.

METHODS AND RESULTS

In 120 patients (20 without regurgitation, 19 with aortic regurgitation, and 81 with mitral regurgitation), the stroke volume through the mitral annulus and left ventricular outflow tract were measured using pulsed-wave Doppler concurrently with left ventricular stroke volume calculated using left ventricular volumes measured by two-dimensional echocardiography Simpson's biapical method. Regurgitant volume and fraction were thus computed using Doppler or ventricular methods. In normal patients there were good correlations between Doppler and left ventricular measurements of stroke volume. Doppler regurgitant volume and fraction were 4.4 +/- 4.4 mL and 5.3 +/- 4.5%, respectively. In patients with aortic regurgitation, there were good correlations between Doppler and left ventricular measurements of stroke volume, regurgitant volume, and regurgitant fraction (r = 0.97, r = 0.95, and r = 0.93, respectively; p < 0.0001). In patients with mitral regurgitation, despite good correlations between Doppler and ventricular methods for stroke volume, regurgitant volume, and regurgitant fraction (r = 0.94, r = 0.93, and r = 0.94, respectively; p < 0.001), these variables were overestimated by Doppler. However, in the last 54 patients compared with the first 27, overestimation decreased significantly for regurgitant volume (5 +/- 10 mL versus 18 +/- 27 mL, p < 0.05) and regurgitant fraction (3.3 +/- 6.7% versus 6.2 +/- 6.8%, p = 0.05).

CONCLUSIONS

Quantitative Doppler can be performed in large numbers of patients in a clinical laboratory. Its potential limitation was identified as overestimation of mitral regurgitation, which is overcome with increased experience. Its achieved accuracy in mitral and aortic regurgitation allows measurement not only of regurgitant fraction but most importantly of regurgitant volume.
Electrophysiological effects of high cocaine concentrations on intact canine heart. Evidence for modulation by both heart rate and autonomic nervous system.
Authors: Clarkson C W , Chang C , Stolfi A , George W J , Yamasaki S , Pickoff A S
Published: June 2012

BACKGROUND

Previous clinical reports have suggested that cocaine intoxication may produce severe ventricular arrhythmias due to a direct effect on the heart. However, the effects of high plasma levels of cocaine on the electrophysiology of the heart have not been well characterized and remain poorly understood.

METHODS AND RESULTS

The purpose of this study was to characterize the electrophysiological effects of high doses of cocaine on the in situ dog heart. In dogs anesthetized with morphine and alpha-chloralose, cocaine (2-11 micrograms/mL) increased both atrial and ventricular refractory periods and produced rate-dependent increases in atrial, atrioventricular, His-Purkinje, and ventricular conduction intervals. The time constant for the onset of cocaine's conduction slowing effect following a reduction in pacing cycle length from 400 to 260 msec was approximately two beats, and the time constant for diastolic recovery from conduction slowing was approximately 200 msec, which are similar to values reported for several class Ib antiarrhythmic drugs. Cocaine produced a rate-dependent increase in QT interval that was greatest at high heart rates yet produced no change in the ST (QT-QRS) interval. This suggests that high plasma levels of cocaine delay repolarization primarily via slowing of conduction. Cocaine's effects on both atrioventricular and intraventricular conduction were significantly larger in autonomically blocked than in autonomically intact animals.

CONCLUSIONS

We conclude that high plasma levels of cocaine, similar to those reported in autopsy reports following fatal cocaine overdose in humans, produce significant rate-dependent conduction slowing effects on atrial, atrioventricular, and ventricular conduction in the in situ heart. These rate-dependent effects are intensified following autonomic blockade.
Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after a transient period of global ischemia is accompanied by a stimulation of glucose oxidation.
Authors: Broderick T L , Quinney H A , Barker C C , Lopaschuk G D
Published: June 2012

BACKGROUND

We have previously shown that increasing myocardial carnitine levels in fatty acid-perfused isolated working rat hearts dramatically increases glucose oxidation rates. Since high levels of fatty acids depress reperfusion recovery of ischemic hearts by inhibiting glucose oxidation, we determined what effect carnitine has on glucose oxidation during reperfusion of ischemic hearts.

METHODS AND RESULTS

Isolated working rat hearts were perfused with 11 mM [5-3H/ul-14C]glucose, 1.2 mM palmitate, and 100 microU/ml insulin and subjected to a 35-minute period of global ischemia followed by aerobic reperfusion. Rates of glycolysis and glucose oxidation were determined by measuring tritiated water and 14CO2 production, respectively. Before ischemia, myocardial carnitine content was first increased by perfusing hearts during a 60-minute baseline aerobic perfusion with 10 mM L-carnitine. This resulted in a significant increase in total myocardial carnitine from 4,804 +/- 358 to 9,692 +/- 2,090 nmol/g dry wt (mean +/- SD). Glycolysis rates in carnitine-treated hearts were not significantly altered compared with control hearts during the aerobic perfusion (2,482 +/- 1,173 versus 1,840 +/- 1,365 nmol glucose.g dry wt-1 x min-1, respectively). In contrast, glucose oxidation rates in carnitine-treated hearts were significantly increased before ischemia compared with control hearts (471 +/- 209 versus 158 +/- 75 nmol glucose.g dry wt-1 x min-1, respectively). During reperfusion of previously ischemic hearts, glycolytic rates returned to preischemic values in both carnitine-treated and control hearts. Glucose oxidation rates also recovered to preischemic values in these hearts and remained significantly elevated in carnitine-treated hearts compared with control hearts (283 +/- 113 versus 130 +/- 27 nmol glucose.g dry wt-1 x min-1, respectively). Mechanical recovery in control hearts returned to 44% of preischemic values (measured as heart rate-peak systolic pressure product), whereas in carnitine-treated hearts, mechanical recovery returned to 71% of preischemic values.

CONCLUSIONS

These results suggest that the beneficial effects of carnitine in the ischemic heart can be explained by the actions of this compound on overcoming fatty acid inhibition of glucose oxidation.
Effects of captopril on ischemia and dysfunction of the left ventricle after myocardial infarction.
Authors: Søgaard P , Gøtzsche C O , Ravkilde J , Thygesen K
Published: June 2012

BACKGROUND

Treatment with angiotensin converting enzyme inhibitors has been shown to be beneficial in patients with heart failure and myocardial infarction. Experimental studies have shown beneficial effects on the ischemic myocardium.

METHODS AND RESULTS

The effects of captopril were evaluated in 64 patients with left ventricular dysfunction after myocardial infarction. The patients were randomized at day 7 to either placebo or captopril (50 mg daily) in a double-blind parallel study over a period of 6 months. The patients were followed up by means of ambulatory ECG monitoring, bicycle ergometer testing, and echocardiographic examination. The duration of ST segment depression detected during ambulatory ECG monitoring was lower in the captopril group (87 minutes) than in the placebo group (638 minutes) (p < 0.001), and the number of patients in the captopril group with exercise-induced ST segment depression (p < 0.01) was lower at the completion of the study. The working capacity increased during the study period from 540 +/- 47 seconds to 738 +/- 41 seconds (p < 0.01) in the captopril group and was higher than that in the placebo group (530 +/- 43 seconds, p < 0.01) at the end of the study. Furthermore, a significant dilation of the left ventricular end-diastolic and end-systolic volumes was observed in the placebo group (p < 0.05); this was prevented in the captopril group where, in addition, a reduction in end-systolic volume was observed (p < 0.05).

CONCLUSIONS

Captopril has a favorable effect on the dysfunctioning myocardium after myocardial infarction inasmuch as the ischemic burden is reduced, the working capacity is increased, dilation of the left ventricle is prevented, and systolic function is improved.
Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study.
Authors: Jenner J L , Ordovas J M , Lamon-Fava S , Schaefer M M , Wilson P W , Castelli W P , Schaefer E J
Published: June 2012

BACKGROUND

Lipoprotein(a) [Lp(a)] is an atherogenic particle that structurally resembles a low density lipoprotein (LDL) particle but contains a molecule of apolipoprotein(a) attached to apolipoprotein B-100 by a disulfide bond. Because elevated plasma levels of Lp(a) have been shown to be an independent risk factor for coronary artery disease, it is important to define normal ranges for this lipoprotein.

METHODS AND RESULTS

We have measured Lp(a) in 1,284 men (mean age, 48 +/- 10 years) and 1,394 women (mean age, 48 +/- 10 years) free of cardiovascular and cerebrovascular disease and not on medications known to affect lipids who were seen at the third examination cycle of the Framingham Offspring Study. Plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay, which uses a "capture" monoclonal anti-apo(a) antibody that does not cross-react with plasminogen, and a polyclonal anti-apo(a) antibody conjugated to horseradish peroxidase. The assay was calibrated to total Lp(a) mass. The Lp(a) frequency distribution was highly skewed to the right, with 56% of the values in the 0-10-mg/dL range. Mean plasma Lp(a) concentrations were 14 +/- 17 mg/dL in men and 15 +/- 17 mg/dL in women. Values of more than 38 mg/dL were above the 90th percentile and values of more than 22 mg/dL were above the 75th percentile in both men and women.

CONCLUSIONS

We have determined mean Lp(a) levels for men and women participating in the Framingham Offspring Study. In this population, there was an inverse association between plasma levels of Lp(a) and triglycerides for both sexes (p < 0.006), but triglycerides accounted for only approximately 0.5% of the variation in Lp(a) levels. Associations of Lp(a) levels with total and LDL cholesterol levels were not significant after correction for the estimated contribution of Lp(a) cholesterol to total and LDL cholesterol. After controlling for age, Lp(a) values were 8% greater in postmenopausal women than in premenopausal women, but this difference was not statistically significant. Body mass index, alcohol consumption, cigarette smoking, use of beta-blockers or cholesterol-lowering medications, and use of drugs for the treatment of diabetes and hypertension were not correlated with Lp(a) levels.
Assessment of the human splanchnic venous volume-pressure relation using radionuclide plethysmography. Effect of nitroglycerin.
Authors: Manyari D E , Wang Z , Cohen J , Tyberg J V
Published: June 2012

BACKGROUND

No method exists to assess human splanchnic venous function, the most important region in terms of vascular capacity.

METHODS AND RESULTS

We studied 25 stable patients without heart failure or hypertension to develop a method to assess the splanchnic venous volume-pressure (V-P) relation and to determine the effect of nitroglycerin (GTN). We used blood pool scintigraphy to assess changes in regional splanchnic vascular volume (SVV) and low levels of continuous positive airway pressure (CPAP) to passively alter venous pressure and thus, SVV. We postulated that the relation between SVV and the CPAP used would reflect the capacitance of the splanchnic venous bed and that changes in the position of this relation would provide a relative measurement of any change in capacitance. In 12 patients (group 1), the splanchnic vascular V-P curves were recorded before and 2, 9, and 20 minutes after 0.6 mg sublingual GTN; in eight patients (group 2), recordings were made at similar times before and after sublingual administration of placebo; in five patients (group 3), the hemodynamic effects of CPAP were assessed by means of right and left cardiac catheterization. Right atrial and femoral venous pressures increased (p < 0.001) and cardiac output fell (p < 0.05) during CPAP. There was an apparently linear relation between CPAP and SVV (r = 0.74-0.98); SVV increased an average of 7.4 +/- 2.2% (p < 0.001) by 12 cm H2O CPAP: The splanchnic vascular V-P curves were reproducible with minimal variability in SVV (+/- 2%, p > 0.2) in group 2. After administration of GTN, the splanchnic vascular V-P curve shifted away from the pressure axis in a parallel fashion by an average of 9.4 +/- 5.4% (p < 0.001).

CONCLUSIONS

We have developed a reproducible noninvasive technique that may be used to assess human splanchnic venous V-P relations. We have demonstrated for the first time in humans that GTN exerts its dilatory effect by increasing the unstressed splanchnic venous volume.
Quantitative adenosine 201Tl single-photon emission computed tomography for the early assessment of patients surviving acute myocardial infarction.
Authors: Mahmarian J J , Pratt C M , Nishimura S , Abreu A , Verani M S
Published: June 2012

BACKGROUND

We prospectively investigated whether adenosine 201Tl tomography (SPECT) could determine the extent of coronary artery disease, the presence of jeopardized myocardium, and the risk for in-hospital cardiac events in 120 clinically stable patients early (5 +/- 3 days) after myocardial infarction.

METHODS AND RESULTS

All patients had coronary angiography and SPECT in close proximity. Adenosine SPECT identified 99% of infarct-related arteries and 82% of severely stenosed (> or = 70%) noninfarct arteries. Multivessel disease was accurately predicted in 69% of patients. Sixty-five percent of stenosed noninfarct arteries had matching thallium perfusion defects, and 92% of these were reversible. The specificity of adenosine SPECT was > 90%. Thallium redistribution occurred often within infarct (59%) and noninfarct (92%) zones. The patency status of the arteries, however, did not predict the presence or extent of jeopardized myocardium. The perfusion defect size was larger (p = 0.0001) in patients with (45 +/- 18%) than in those without (22 +/- 15%) in-hospital cardiac events. Furthermore, 90% of patients with events had a > or = 20% perfusion defect compared with only 38% of those without events (p = 0.0001). The positive-predictive accuracy for developing a cardiac event was 70% when the perfusion defect size was > 30%. The ischemic defect also was larger in patients with (19 +/- 14%) than in those without (10 +/- 10%) events (p = 0.001). The positive- and negative-predictive values for developing early postinfarction angina were 43% and 91%, respectively, when the ischemic defect was > 12%.

CONCLUSIONS

In selected low-risk survivors of myocardial infarction, early quantitative adenosine SPECT is safe and accurate in detecting and localizing coronary stenoses, assessing the extent of jeopardized myocardium, and determining subsequent risk for in-hospital cardiac events.
Comparison of resetting and entrainment of uniform sustained ventricular tachycardia. Further insights into the characteristics of the excitable gap.
Authors: Callans D J , Hook B G , Josephson M E
Published: June 2012

BACKGROUND

Resetting and entrainment have both been used to characterize the electrophysiological properties of the reentrant circuit in ventricular tachycardia. Several entrainment studies have suggested that the circuit has decremental properties, because the return cycle increases at faster pacing rates. Resetting, however, demonstrates a fully excitable gap in the majority of tachycardias.

METHODS AND RESULTS

The response to resetting and overdrive pacing was analyzed in 18 ventricular tachycardias. Resetting demonstrated some duration of a fully excitable gap in 14 of 18 tachycardias. Overdrive pacing was performed at several cycle lengths with an incremental number of stimuli (1-15 beats) such that the first beat that interacted with the tachycardia (the nth beat) could be identified. The return cycles measured during resetting and the nth beat of pacing were identical (r = 0.99). At relatively long paced cycle lengths, paced beats after the nth beat resulted in a constant return cycle in most tachycardias with a fully excitable gap. At rapid paced cycle lengths, an increase in the return cycle from the nth to the nth + 1 beat was associated with progressive prolongation in the return cycle with each incremental paced beat until a longer equilibrium return cycle was reached or the tachycardia terminated in response to pacing.

CONCLUSIONS

We propose that the responses to resetting and overdrive pacing with or without entrainment appear to provide conflicting information about the characteristics of the circuit because they in fact measure entirely different electrophysiological parameters. The nth beat of pacing foreshortens the excitable gap to the extent that it arrives prematurely. Subsequent paced beats interact with an altered tachycardia circuit that has had less time to recover excitability. Resetting is the interaction of a single paced beat with the tachycardia and, as such, provides a more accurate assessment of the characteristics of the unaltered tachycardia circuit.
Does obesity influence early target organ damage in hypertensive patients?
Authors: Schmieder R E , Messerli F H
Published: June 2012

BACKGROUND

Various prospective studies have found that lean hypertensive patients have greater cardiovascular morbidity and mortality than obese hypertensive subjects. It was therefore hypothesized that hypertension is more benign when associated with obesity. In the present study, we evaluated effects of obesity on early target organ damage in patients with essential hypertension.

METHODS AND RESULTS

In a total of 207 subjects, systemic and renal hemodynamics as well as left ventricular structure and function were assessed by measuring cardiac output (indocyanine green dye dilution), renal blood flow (clearance of 131I paraimmunohippuric acid), and mean arterial pressure (invasively) and by two-dimensionally guided M-mode echocardiographic findings. Systemic and renal vascular resistance, compliance of the large arteries evaluated by the stroke volume/pulse pressure index, and left ventricular mass served as parameters for early target organ damage. All individuals were categorized into four groups: lean and obese normotensive as well as lean and obese hypertensive subjects. In obese hypertensive patients, total peripheral resistance was significantly lower and stroke volume/pulse pressure index was higher than in the lean hypertensive group, almost reaching values of normotensive control subjects. No effect of obesity on the renal circulation was noted, whereas in hypertension, renal vascular resistance was elevated. The degree of left ventricular hypertrophy was more pronounced in the hypertensive groups than in their normotensive counterparts and progressively increased with obesity. Nevertheless, in obese hypertensive patients, left ventricular function, as measured by fractional fiber shortening and velocity of circumferential fiber shortening, was maintained despite the fact that the heart had been exposed to the double burden of an increased preload (obesity) and afterload (hypertension).

CONCLUSIONS

Obesity had a disparate effect on target organs in hypertension. At rest, obesity seemed to mitigate cardiovascular changes in the systemic vascular bed caused by hypertension. However, no such mitigation was observed in the renal vasculature, and left ventricular hypertrophy was even exacerbated by the presence of obesity. Our findings in part negate the concept that obesity is able to exert a protective effect on early target organ damage in hypertensive patients and, in particular, on the heart.
Time course of restenosis during the first year after emergency coronary stenting.
Authors: Kastrati A , Schömig A , Dietz R , Neumann F J , Richardt G
Published: June 2012

BACKGROUND

Prevention of abrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) represents one of the current indications for intracoronary stent implantation. After the procedure, the stented segment undergoes luminal changes that may lead to late restenosis. This study was undertaken to assess the time course of luminal changes during the first year after emergency placement of coronary stents.

METHODS AND RESULTS

Coronary stenting was indicated in patients with present or threatened vessel closure secondary to large dissections after PTCA. From June 1989 to May 1991, 82 patients who received Palmaz-Schatz stents and did not have early vessel occlusion after stenting were enrolled into a serial angiographic follow-up study. Coronary normal reference diameter and minimal luminal diameter were measured with an automated edge detection technique. Patients who underwent repeat PTCA for restenosis were excluded from further serial angiography. The restudy rate at 3, 6, and 12 months was 96%, 81%, and 90% of the eligible patients, respectively. The incidence of restenosis (defined as a diameter stenosis > or = 50%) was 22.0% at 3 months, 31.9% at 6 months, and 33.2% at 12 months. Minimal luminal diameter was increased from 0.66 +/- 0.32 mm before to 2.85 +/- 0.43 mm immediately after stenting. It was 0.46 +/- 0.31 mm smaller than the diameter of the maximally inflated balloon during the procedure. The reduction in minimal luminal diameter was 0.80 +/- 0.69 mm (p = 0.0001) for the first 3 months, 0.29 +/- 0.52 mm (p = 0.0001) between 3 and 6 months, and 0.13 +/- 0.32 mm (p = 0.01) for the last 6 months. The percentage of patients who presented a significant change in minimal luminal diameter (defined as > 0.60 mm) declined from 50.6% during the first 3 months and 18.9% between 3 and 6 months to 6.5% for the period between 6 and 12 months.

CONCLUSIONS

The incidence and the time course of restenosis after emergency coronary stenting are similar to that reported for conventional PTCA. Coronary lumen dimensions demonstrated a peak change at 3 months and remained mostly stable after the first 6 months.
Quantification of left-to-right atrial shunting and defect size after balloon mitral commissurotomy using biplane transesophageal echocardiography, color flow Doppler mapping, and the principle of proximal flow convergence.
Authors: Rittoo D , Sutherland G R , Shaw T R
Published: June 2012

BACKGROUND

The flow convergence region (FCR), a zone of progressive laminar velocity acceleration, can be imaged by color Doppler proximal to stenotic and regurgitant orifices. Theoretically, FCR proximal to a discrete circular and planar orifice consists of concentric hemispheric shells of equal and accelerating velocities centered at the orifice. According to the continuity principle, flow rate across any of these isovelocity surfaces equals flow rate through the orifice. The aim of this study was to investigate whether these principles could be applied to quantify left-to-right shunting and the size of atrial septal defects after balloon mitral commissurotomy.

METHODS AND RESULTS

Biplane transesophageal echocardiography (TEE) with color flow imaging was performed on 36 consecutive patients (mean age, 57 +/- 16 years; range, 14-78 years) immediately before and within 24 hours of balloon (Inoue, n = 33; Mansfield, n = 3) mitral commissurotomy. Left-to-right atrial shunting was detected by TEE in 33 patients (92%) and by oximetry in 11 patients (31%). The radius r of FCR was measured from the first aliasing limit, at a Nyquist velocity reduced to 11 cm/sec by zero-shifting, to the orifice in the atrial septum. FCR was assumed to be hemispherical. Hence, flow rate (Q) was calculated as 2 pi r2 Vr, where Vr is the velocity at a radial distance r. The velocity profile of transatrial flow was assessed by means of high pulse repetition frequency, from which the maximum flow velocity (Vp) and the velocity-time integral (VTI) were obtained. The flow area of the atrial septal defect was calculated as Qm, the maximal flow rate, divided by Vp. Hence, shunt flow was calculated as flow area x VTI x heart rate. FCR was analyzed in two orthogonal planes. Mean Qm (38.1 +/- 26.5 versus 5.3 +/- 2.7 mL/sec), flow area (22.1 +/- 11.2 versus 4.4 +/- 2.0 mm2), and shunt flow (1,590 +/- 1,070 versus 200 +/- 130 mL/min) on transverse plane imaging were all significantly higher in patients with shunts detected by oximetry than in those without. Similar results were obtained from longitudinal plane imaging. Qm correlated well with oximetric shunt flow (r = 0.89-0.94, p < 0.001) and shunt ratio (r = 0.91-0.94, p < 0.001). Flow area correlated closely (r = 0.93-0.94, p < 0.001) with area determined by direct measurement from two-dimensional echocardiography. Shunt flow determined by FCR also correlated closely (r = 0.94-0.98, p < 0.001) with that determined by oximetry and that derived from two-dimensional echocardiography and pulsed Doppler (r = 0.96, p < 0.001).

CONCLUSIONS

The flow convergence region imaged by TEE color flow mapping provides new and accurate quantitative information on atrial shunt flow and defect size after balloon mitral valvotomy. It is a quick, reliable, and fairly simple method that can be readily incorporated into routine clinical practice.
Scintigraphic pattern of regional cardiac sympathetic innervation in patients with familial long QT syndrome using positron emission tomography.
Authors: Calkins H , Lehmann M H , Allman K , Wieland D , Schwaiger M
Published: June 2012

BACKGROUND

The purpose of this study was to determine whether scintigraphic evidence of cardiac sympathetic neuronal dysinnervation is present in patients with the familial long QT syndrome. The "sympathetic imbalance" hypothesis for the familial long QT syndrome proposes that the long QT syndrome results from a congenital imbalance of sympathetic innervation of the heart caused by lower-than-normal right cardiac sympathetic activity. Although the majority of clinical features of the long QT syndrome can be understood according to this hypothesis, its validity has never been shown. Noninvasive scintigraphic evaluation of the pattern of sympathetic innervation of the heart has recently become possible with catecholamine analogues that can be taken up by sympathetic nerve terminals: radioiodinated metaiodobenzyl guanidine or C-11 hydroxyephedrine (HED).

METHODS AND RESULTS

Nine affected patients, each from a separate family with familial long QT syndrome, were enrolled in this study (three men, six women; mean age, 39 +/- 16 years). Scintigraphic evaluation of the pattern of cardiac sympathetic innervation in each patient was performed with HED in conjunction with positron emission tomography. The results of scintigraphic imaging in these patients were compared with those obtained in 14 asymptomatic volunteers. Scintigraphic evaluation demonstrated that HED retention index and HED uptake normalized to blood flow were no different in patients with the familial long QT syndrome than in normal control patients.

CONCLUSIONS

Patients with the long QT syndrome have normal cardiac sympathetic innervation as assessed by HED. This finding, although not incompatible with the sympathetic imbalance hypothesis of the long QT syndrome, suggests that if a decrease in right sympathetic activity is present in patients with familial long QT syndrome, it is unlikely to be attributed to an abnormal distribution of cardiac sympathetic nerves.
Acute intravenous cocaine causes transient depression followed by enhanced left ventricular function in conscious dogs.
Authors: Stambler B S , Komamura K , Ihara T , Shannon R P
Published: June 2012

BACKGROUND

Prior studies in experimental canine models have demonstrated that intravenous cocaine administration causes myocardial depression. The purpose of the present study was to establish the mechanisms of cocaine's actions on myocardial and left ventricular performance after single intravenous bolus doses in conscious, chronically instrumented dogs, in which the full autonomic influences of cocaine would be manifest.

METHODS AND RESULTS

In the intact state, cocaine (1 mg/kg) caused a transient decrease in left ventricular dP/dt (baseline; 3,086 +/- 107 mm Hg/sec; 2.5 minutes, 2,649 +/- 114 mm Hg; p < 0.05) followed by a 25 +/- 4% increase in left ventricular dP/dt that peaked at 15 minutes (left ventricular dP/dt, 3,751 +/- 127 mm Hg/sec, p < 0.01) and remained elevated during the 30-minute period of observation. Both the initial depression and the sustained increase in left ventricular contractile response were dose related. The increase in left ventricular dP/dt persisted under circumstances in which the responses were normalized for changes in heart rate and preload that accompanied cocaine administration. The positive inotropic effects were abolished by full autonomic or selective beta-adrenergic blockades. Finally, both cardiac output (baseline, 2,461 +/- 142 min/mL; peak [5 minutes], 3,434 +/- 218 mL/min; p < 0.05) and left ventricular stroke work (baseline, 39 +/- 5 g.m; peak, 49 +/- 6 g.m; p < 0.05) were increased at all times after cocaine administration, suggesting that pump performance was enhanced, despite early reductions in myocardial contractility. Similarly, indexes of early diastolic filling were enhanced despite transient early prolongation in isovolumic relaxation.

CONCLUSIONS

Acute intravenous cocaine administration (0.1-2 mg/kg) has a biphasic effect on myocardial and left ventricular function with a transient depression followed by significant sustained increases in left ventricular contractility. The results are in keeping with an early local effect followed by significant adrenergic stimulation, which may be obscured by anesthesia or masked by changes in loading conditions.
Role of oscillatory potential and pacemaker shifts in digitalis intoxication of the sinoatrial node.
Authors: Gonzalez M D , Vassalle M
Published: June 2012

BACKGROUND

Digitalis intoxication causes tachycardia, pacemaker shifts, and conduction disturbances in the sinoatrial (SA) node, but the mechanisms underlying these changes have not been clarified. We studied the role played by oscillatory potentials, electrical inhomogeneity, and calcium overload in cardiac steroid intoxication of the SA node.

METHODS AND RESULTS

Guinea pig SA nodes (isolated from atrial tissue) were perfused in vitro. Transmembrane potentials and force were recorded. Strophanthidin (1 mumol/L) induced minor changes, although it was perfused for more than 30 minutes. In contrast, ouabain (0.5 mumol/L) and digoxin (1 mumol/L) intoxicated the SA node in 10-20 minutes. Ouabain and digoxin increased spontaneous rate and slope of diastolic depolarization, shifted the plateau to more negative values, and decreased the maximum diastolic potential. These cardiac steroids increased and then decreased contractile force and eventually caused the action potential and twitch to become irregular in amplitude and rhythm. In the presence of acetylcholine (ACh, 0.01-1 mumol/L), cardiac steroids decreased the resting potential, caused spontaneous activity, and increased force and, eventually, oscillatory potentials (Vos) and aftercontractions as well as overdrive excitation. To make the SA node electrically homogeneous (only slow responses), the SA node was perfused with high extracellular potassium concentration (with and without norepinephrine), tetrodotoxin (2.61 mumol/L), or lidocaine (50 mumol/L). Adding ouabain or digoxin to these solutions increased the rate but far less than in Tyrode's solution. Recovery in Tyrode's solution initially caused fast and irregular rhythms, which then subsided. Low extracellular calcium concentration ([Ca]o) (0.54 mmol/L) decreased force; adding ouabain markedly increased force and induced Vos. High [Ca]o (8.1 mmol/L) increased force; adding ouabain decreased force and made action potentials as well as contractions quite irregular.

CONCLUSIONS

Ouabain and digoxin quickly intoxicate the SA node by inducing calcium overload and its manifestations (Vos, decrease in contractile force and aftercontractions), whereas strophanthidin does not, possibly because of the lack of a sugar moiety. The intoxication is less pronounced when sodium influx is decreased (slow responses), and this accounts for the shifts from dominant to subsidiary pacemakers. Marked conduction disturbances result from calcium overload, leading to the fractionation of SA node activity.
X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus.
Authors: Towbin J A , Hejtmancik J F , Brink P , Gelb B , Zhu X M , Chamberlain J S , McCabe E R , Swift M
Published: June 2012

BACKGROUND

X-linked cardiomyopathy (XLCM) is a rapidly progressive primary myocardial disorder presenting in teenage males as congestive heart failure. Manifesting female carriers have later onset (fifth decade) and slower progression. The purpose of this study was to localize the XLCM gene locus in two families using molecular genetic techniques.

METHODS AND RESULTS

Linkage analysis using 60 X-chromosome-specific DNA markers was performed in a previously reported large XLCM pedigree and a smaller new pedigree. Two-point and multipoint linkage was calculated using the LINKAGE computer program package. Deletion analysis included multiplex polymerase chain reaction (PCR). Dystrophin protein was evaluated by Western blotting with N-terminal and C-terminal dystrophin antibody. Linkage of XLCM to the centromeric portion of the dystrophin or Duchenne muscular dystrophy (DMD) locus at Xp21 was demonstrated with combined maximum logarithm of the scores of +4.33, theta = 0 with probe XJ1.1 (DXS206) using two-point linkage and +4.81 at XJ1.1 with multipoint linkage analysis. LOD scores calculated using other proximal DMD genomic and cDNA probes and polymerase chain reaction polymorphisms supported linkage. No deletions were observed. Abnormalities of cardiac dystrophin were shown by Western blotting with N-terminal dystrophin antibody, whereas skeletal muscle dystrophin was normal, suggesting primary involvement of the DMD gene with preferential involvement of cardiac muscle.

CONCLUSIONS

XLCM is due to an abnormality within the centromeric half of the dystrophin genomic region in heart. This abnormality could be due to 1) a point mutation in the 5' region of the DMD coding sequence preferentially affecting cardiac function, 2) a cardiac-specific promoter mutation that alters expression in this tissue, 3) splicing abnormalities, resulting in an abnormal cardiac protein, or 4) deletion mutations undetectable by Southern and multiplex polymerase chain reaction analysis.
Increased left ventricular mass after thoracotomy and pericardiotomy. A role for relief of pericardial constraint?
Authors: Tischler M D , Rowan M , LeWinter M M
Published: June 2012

BACKGROUND

Myocardial stretch and increased ventricular filling can lead to increased rates of myocardial protein synthesis. In animal studies, left ventricular mass increases after pericardiectomy, suggesting relief of a biologically meaningful restraining role and a resultant stimulus for growth. The present study was designed to test the hypothesis that combined thoracotomy and pericardiotomy leads to left ventricular hypertrophy in patients with normal left ventricular ejection fraction undergoing elective bypass surgery.

METHODS AND RESULTS

Twenty-five patients with normal left ventricular ejection fraction without active myocardial ischemia underwent Doppler and quantitative two-dimensional echocardiography 1 day before and 6 weeks and 7 months after elective coronary artery bypass surgery. The pericardium was left widely incised in all patients. Left ventricular end-systolic volume, end-diastolic volume, stroke volume, ejection fraction, end-systolic circumferential wall stress, and mass were measured. Left ventricular end-diastolic volume index increased from 51 +/- 11 mL/m2 to 62 +/- 14 mL/m2 (p < 0.05) at 6 weeks and to 66 +/- 14 mL/m2 (p < 0.05 versus baseline, p = NS versus 6 weeks) at 7 months. Left ventricular mass index increased from 109 +/- 23 g/m2 to 127 +/- 24 g/m2 (p < 0.05) at 6 weeks and to 131 +/- 23 g/m2 (p < 0.05 versus baseline, p = NS versus 6 weeks) at 7 months. There were no changes in systolic or diastolic blood pressures, end-systolic circumferential wall stress, or end-systolic volume.

CONCLUSIONS

Patients with normal left ventricular ejection fraction develop increases in left ventricular end-diastolic volume and mass after coronary artery bypass surgery. These findings support the hypothesis that the increase in left ventricular end-diastolic volume associated with thoracotomy and pericardiotomy leads to myocardial growth and an increase in left ventricular mass.
Intimal thickening of the coronary arteries in infants in relation to family history of coronary artery disease.
Authors: Kaprio J , Norio R , Pesonen E , Sarna S
Published: June 2012

BACKGROUND

Intimal thickenings of the coronary arteries of newborn children are composed mainly of smooth muscle cell proliferations. To investigate whether thickening of the intima in infants is associated with a family history of coronary artery disease (CAD), we studied the relation of coronary death of grandparents to intimal thickening of 136 infants.

METHODS AND RESULTS

The length of internal elastic lamina of the artery and the areas of arterial layers in cross section were measured, and the arteries were transformed to idealized round circles. Intimal thickening was assessed as the degree of luminal narrowing (ratio of intimal area to the area on the luminal side of the arterial media). Among 136 infants, luminal narrowing varied between 0% and 58%. CAD deaths accounted for 108 of the total 281 deaths among the grandparents of the infants. Family history of CAD (defined as at least one CAD death among the four grandparents) was positive for 77 infants. Family history of CAD was significantly more common in the infants with luminal narrowing of both the left and right coronary arteries compared with the infants with no narrowing in at least one artery (odds ratio adjusted for sex, infection status, and age of infant, 5.69; 95% confidence interval, 1.46-22.2). After adjustment for sex and age, infants with both a positive family history and presence of infection had an increased degree of luminal narrowing compared with infants with a negative family history and no infection.

CONCLUSIONS

The association of coronary artery intimal thickening in infancy with family history of CAD suggests that intimal thickening is a morphological manifestation of predisposition to CAD.
Age thresholds for prophylactic replacement of Björk-Shiley convexo-concave heart valves. A clinical and economic evaluation.
Authors: van der Meulen J H , Steyerberg E W , van der Graaf Y , van Herwerden L A , Verbaan C J , Defauw J J , Habbema J D
Published: June 2012

BACKGROUND

Björk-Shiley convexo-concave heart valves have an increased risk of mechanical failure. One might consider prophylactic rereplacement as a preventive measure to avert the disastrous consequences of these failures. We investigated the effect that prophylactic rereplacement has on survival of individual patients and on the medical costs.

METHODS AND RESULTS

Quantitative estimates for the surgical risks of prophylactic replacement of Björk-Shiley valves, long-term survival, and the risk of outlet strut fracture were derived insofar as possible from a detailed analysis of a follow-up study conducted in The Netherlands, including 2303 patients with a mean follow-up of 6.6 years. On the basis of these estimates, we calculated life expectancy with and without prophylactic replacement. For the various valve types, age thresholds were determined below which rereplacement prolongs (discounted quality-adjusted) life expectancy. We also calculated the cost per year of life gained as a function of age. The age thresholds below which prophylactic rereplacement increases life expectancy (expressed in simple future years of life) for male patients without comorbidity, if the surgical mortality after rereplacement is equivalent to that of primary replacement, are 27, 48, 51, and 65 years for small and large 60 degrees and for small and large 70 degrees mitral valves, respectively. For aortic valves, these age thresholds lie somewhat higher: 39, 52, 56, and 76 years, respectively. Repeat analyses indicated that for women, all age thresholds lie about 1 or 2 years higher. These age thresholds decrease considerably if the surgical mortality after rereplacement is considered to be higher after prophylactic rereplacement than after primary replacement or if comorbidity is present. The costs per discounted and quality-adjusted year of life gained depend on type and position of the Björk-Shiley convexo-concave heart valve and rise steeply as the patient's age approaches the threshold for rereplacement.

CONCLUSIONS

The results of the Dutch follow-up study allow guidance for prophylactic replacement of the Björk-Shiley convexo-concave valve on an individual basis. Rereplacement compares favorably with expectant management in some patient subgroups with both 60 degrees and 70 degrees valves. Age thresholds may serve as a first step in identifying patients in whom rereplacement might be beneficial.
Heparin accelerates coronary collateral development in a porcine model of coronary artery occlusion.
Authors: Carroll S M , White F C , Roth D M , Bloor C M
Published: June 2012

BACKGROUND

Coronary collaterals develop in response to an ischemic stimulus. However, collateral growth is not sufficient to result in the complete recovery of coronary reserves. Using a porcine model of gradual coronary artery occlusion, we investigated the effect of continuous heparin infusion on coronary collateral development.

METHODS AND RESULTS

We placed ameroid constrictors on the left circumflex coronary artery of 16 minipigs; the ameroid constrictors completely occluded the left circumflex coronary artery at 10 +/- 1 days. Half of the animals also were instrumented with subcutaneously placed osmotic pumps and catheters that delivered heparin (300 units/h) into the external jugular vein. At 2, 3, and 4 weeks, we assessed blood flow at rest and during vasodilation using radioactive microspheres. Our results indicate that the animals receiving heparin restored resting myocardial blood flow to normal levels at or before 2 weeks; in contrast, we did not see normal resting myocardial blood flow levels in the untreated-ameroid animals until 3 weeks. Under vasodilated conditions, untreated-ameroid animals experienced a severe loss of coronary reserves at 2 weeks. Although this improved with time, these animals still were significantly underperfused at 4 weeks. In contrast, in the heparin-treated animals, coronary reserves returned to near-normal levels between 3 and 4 weeks. In addition, infarct size was significantly smaller in the heparin-treated animals.

CONCLUSIONS

These experiments suggest that the administration of heparin in the early phases of gradual coronary occlusion accelerates the rate of return of normal blood flow under resting conditions, substantially increases the recovery of coronary reserve, and reduces the risk of infarction.
Enhanced revascularization of the ischemic limb by angiogenic therapy.
Authors: Pu L Q , Sniderman A D , Brassard R , Lachapelle K J , Graham A M , Lisbona R , Symes J F
Published: June 2012

BACKGROUND

This study tests the efficacy of an angiogenic growth factor, endothelial cell growth factor, in a rabbit model of persistent hindlimb ischemia.

METHODS AND RESULTS

Ischemia was induced in the left hindlimb of 22 New Zealand White rabbits by ligation of the distal external iliac artery and complete excision of the common and superficial femoral arteries. Two groups of animals were studied: Group 1 consisted of 11 animals who for 10 days received daily intramuscular injections of 4 mg of endothelial cell growth factor beginning on postoperative day 11, and group 2 consisted of 11 animals who underwent the same surgical ischemic procedure but received only injections of saline daily for the same postoperative period. Perfusion of the ischemic left limb was compared with the normal right limb in each animal on postoperative days 10, 20, 30, and 40 using the calf blood pressure ratio, 99mTc macroaggregate radioisotopic perfusion scans, and serial angiography. Neovascularization in the left thigh at day 40 was quantified from the angiograms. Each technique documented that animals in group 1 had significantly better perfusion than animals in group 2; that is, the calf pressure ratio was higher in group 1 than in group 2 (0.56 versus 0.32 at day 20, 0.64 versus 0.44 at day 30, and 0.70 versus 0.50, P < .0001), and the calf radioisotopic perfusion ratio was also higher in group 1 than in group 2 (0.88 versus 0.74 at day 20, P < .02; 0.93 versus 0.76 at day 30, and 0.96 versus 0.79 at day 40, P < .008). Angiographic studies correlated well with these results demonstrating much earlier distal arterial reconstitution and enhanced neovascularization (23.8 versus 9.0 vessels, P < .007).

CONCLUSIONS

The data clearly indicate that an angiogenic growth factor, endothelial cell growth factor, promotes revascularization in this experimental ischemic hindlimb model, raising the possibility that in the future such agents might be of value in humans.
Glibenclamide antagonizes adenosine A1 receptor-mediated cardioprotection in stunned canine myocardium.
Authors: Yao Z , Gross G J
Published: June 2012

BACKGROUND

The main objective of the present study was to determine the role of adenosine in the development of myocardial stunning following multiple, brief periods of coronary artery occlusion as well as the subtype of adenosine receptor (A1 or A2) involved. A second objective was to determine if there was an interaction between the adenosine A1 receptor and the ATP-dependent K channel (KATP).

METHODS AND RESULTS

The effects of the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and agonist cyclopentyladenosine (CPA), the selective A2 receptor agonist CGS 21680, and the KATP channel blocker glibenclamide on myocardial stunning produced by repetitive coronary artery occlusions were studied in barbital-anesthetized dogs. Regional segment function was measured with sonomicrometry. Under control conditions, six 5-minute periods of coronary occlusion interspersed with 10-minute periods of reperfusion and ultimately followed by 2 hours of reperfusion produced regional segment dysfunction. Pretreatment with intravenous infusion of CPA (2.0 micrograms.kg-1.min-1) improved percent segment shortening throughout reperfusion, whereas pretreatment with DPCPX (1.0 mg/kg i.v. bolus) significantly worsened the recovery of postischemic contractile function. In contrast, neither DPCPX nor CPA had any effect on the recovery of contractile function when administered before the second coronary occlusion. Furthermore, pretreatment with CGS 21680 (0.2 micrograms.kg-1.min-1) did not affect the recovery of percent segment shortening. In addition, pretreatment with a low dose of glibenclamide (0.1 mg/kg) had no effect on percent segment shortening by itself but completely abolished the beneficial effect of CPA. Importantly, the effects of the various agents on percent segment shortening were independent of difference in systemic hemodynamics, collateral blood flow, or ischemic bed size.

CONCLUSIONS

These results suggest that stimulation of myocardial adenosine A1 receptors, particularly when induced by the initial coronary artery occlusion, is cardioprotective during repetitive, brief periods of coronary artery occlusion and that these beneficial actions may be partially mediated via a glibenclamide-sensitive mechanism, possibly opening of myocardial KATP channels.