bluuebunny/crossref_metadata_2025 huggingface dataset:
Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy.
Authors: Bolognese L , Sarasso G , Bongo A S , Rossi L , Aralda D , Piccinino C , Rossi P
Published: June 2012

BACKGROUND

We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy.

METHODS AND RESULTS

Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01).

CONCLUSIONS

DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention.
Hyperinsulinemia, sex, and risk of atherosclerotic cardiovascular disease.
Authors: Modan M , Or J , Karasik A , Drory Y , Fuchs Z , Lusky A , Chetrit A , Halkin H
Published: June 2012

BACKGROUND

The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies.

METHODS AND RESULTS

In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids.

CONCLUSIONS

Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.
Localization of breakthrough site of canine monomorphic ventricular tachycardia by pacemapping. A vectorial approach.
Authors: Lin J L , Wilber D J , Du D , Pearlman J , Ruskin J N , Garan H
Published: June 2012

BACKGROUND

The precision and limitations of ventricular pacemapping as a method to localize the site of earliest breakthrough of ventricular tachycardia (VT) were investigated in a canine model of experimental myocardial infarction.

METHODS AND RESULTS

Forty-one episodes of VT induced in 10 animals were mapped using a standard grid of 64 endocardial and epicardial bipolar electrodes to determine the site of earliest endocardial or epicardial breakthrough of activation during VT. Each of these 64 recording sites was also used for ventricular pacing during sinus rhythm at cycle lengths comparable to those of the VTs. Orthogonal X, Y, and Z Frank electrocardiographic (ECG) leads were recorded during all episodes of VT and ventricular pacing from all sites after the chest was closed in all animals. Surface ECG waveforms corresponding to each VT and each ventricular pacing were compared pairwise by measuring the Euclidean metric difference between the VT and ventricular pacing vectors with the orthogonal ECG leads as their X, Y, and Z components. The pacing site that generated the vector most similar to VT vector (smallest vectorial difference) was defined as the predicted breakthrough site. This predicted site of breakthrough was identical to the actual site of breakthrough determined by activation sequence mapping during VT for only nine VTs (22%). However, for an additional 27 VTs (66%), the observed and predicted breakthrough locations were at adjacent (1 cm or less apart) recording sites. For five VTs (12%), the two sites were remote, the distance between them exceeding 1 cm.

CONCLUSIONS

In this model, locating the breakthrough site by pacemapping is exact in only a small minority of VTs. However, when orthogonal surface ECG leads are used for comparison, pacemapping can predict the site of earliest breakthrough during VT with a 1-cm resolution in the majority of VTs.
Effect of altered activation sequence on epicardial QRST area and refractory period in dogs.
Authors: Hanashima K , Kubota I , Ozawa T , Shibata T , Yamaki M , Ikeda K , Yasui S
Published: June 2012

BACKGROUND

We investigated the effects of activation sequence on cardiac surface QRST areas and refractory periods in experiments on dogs.

METHODS AND RESULTS

Right and left ventricular pacings were performed, and the pacing site was altered every 6 minutes. After 4 minutes of a given pacing, 54 unipolar electrograms distributed over the entire cardiac surface were recorded. Next, refractory periods at electrode sites near pacing electrodes were measured. Paired right ventricular/left ventricular (RV/LV) pacing data were obtained six or seven times in each sample. Although the QRST isoarea maps during the two activation orders were qualitatively similar, it was recognized consistently from the right ventricle-left ventricle difference map that leads around the RV free wall had positive values and that leads around the LV free wall and apex had negative values. Compared with the same leads at RV and LV pacing, QRST areas were larger when pacing sites were near the leads. The local QRST areas of individual leads at which we measured local refractory period were consistently larger during drive from proximal pacing sites than during drive from distant pacing sites. Refractory periods were consistently longer during proximal pacing than during distal pacing, and there was a positive correlation between change in local QRST area and change in refractory period (r = 0.64) during altered activation sequence, whereas there was an inverse correlation between change in QRST area and change in refractory period (r = -0.91) during localized myocardial warming.

CONCLUSIONS

Both local QRST areas and local refractory periods were dependent on the activation sequence, and there was a positive correlation between QRST areas and refractory periods during various activation sequences compared with localized myocardial warming.
Effects of an increase in intracellular free [Mg2+] after myocardial stunning on sarcoplasmic reticulum Ca2+ transport.
Authors: Krause S M , Rozanski D
Published: June 2012

BACKGROUND

Myocardial stunning has been associated with a greater than twofold increase in intracellular free [Mg2+] from 0.6 to 1.5 mM. The effect of this increase in free [Mg2+] on the function of the sarcoplasmic reticulum (SR) Ca2+ pump was assessed in SR isolated from Langendorff perfused, isovolumic rabbit hearts after 15 minutes of global ischemia.

METHODS AND RESULTS

Our results indicate that myocardial stunning results in a shift in the Ca2+ sensitivity of oxalate-supported, Ca2+ transport over the entire range of free [Ca2+] associated with the cardiac cycle. Using 0.6 mM free Mg2+ as control, maximal rates of Ca2+ transport occurred at 1 microM free Ca2+ (control, 519 +/- 32; stunned, 337 +/- 37 nmol Ca2+.min-1.mg-1). At 0.56 microM free Ca2+, SR Ca2+ transport was reduced from a control of 351 +/- 49 to 263 +/- 12 nmol Ca2+.min-1.mg-1 at 0.6 mM free [Mg2+]. Moreover, an increase in the free [Mg2+] from 0.6 to 1.5 mM results in a greater shift in the Ca2+ activation curve with no change in the level of maximal activation. Ca2+ transport at 0.56 microM free Ca2+ was shifted in the stunned SR from 263 +/- 12 to 138 +/- 29 nmol Ca2+.min-1.mg-1 at 0.6 and 1.5 mM free Mg2+, respectively.

CONCLUSIONS

These results indicate that an increase in free [Mg2+] after stunning in combination with the inherent defect in the SR Ca2+ ATPase may reduce the ability of the cell to regulate Ca2+ to a greater extent than previously observed. This impairment in Ca2+ regulatory function may contribute directly to the increase in diastolic tone and indirectly to the reduced systolic function characteristic of the stunned myocardium.
Myocardial oxygen consumption and the left ventricular pressure-volume area in normal and hypertrophic canine hearts.
Authors: Izzi G , Zile M R , Gaasch W H
Published: June 2012

BACKGROUND

To assess and compare the energy demands of normal and hypertrophic hearts, we defined the relation between myocardial oxygen consumption (MVO2, an index of the energy consumed by contraction) and the left ventricular pressure-volume area (PVA, an index of the total mechanical energy generated by contraction) in eight normal and eight hypertrophic (aortic band model) dog hearts; MVO2 was also measured in the nonworking (empty beating) and basal (potassium arrest) states.

METHODS AND RESULTS

The hearts were studied in an isolated, blood-perfused heart apparatus. The slope of the MVO2-PVA relation (the inverse of which reflects myofibrillar efficiency) was similar in normal and hypertrophic hearts (3.89 +/- 1.91 and 4.19 +/- 1.25 ml O2/mm Hg.ml.10(5), p = NS). The MVO2 in empty beating (0.038 +/- 0.006 and 0.041 +/- 0.015 ml/beat/100 g, p = NS) and potassium-arrested (1.95 +/- 0.06 and 1.98 +/- 0.20 ml/min/100 g, p = NS) hearts was likewise similar in the two groups.

CONCLUSIONS

Basal and nonworking energy demands and working efficiencies of hypertrophic hearts are equivalent to those of normal hearts.
Muscle carnitine deficiency in patients with severe peripheral vascular disease.
Authors: Brevetti G , Angelini C , Rosa M , Carrozzo R , Perna S , Corsi M , Matarazzo A , Marcialis A
Published: June 2012

BACKGROUND

This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease.

METHODS AND RESULTS

Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L-propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities.

CONCLUSIONS

Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease.
QT interval prolongation predicts cardiovascular mortality in an apparently healthy population.
Authors: Schouten E G , Dekker J M , Meppelink P , Kok F J , Vandenbroucke J P , Pool J
Published: June 2012

BACKGROUND

In myocardial infarction patients, heart rate-adjusted QT interval (QTc), an electrocardiographic indicator of sympathetic balance, is prognostic for survival.

METHODS AND RESULTS

In a 28-year follow-up, the association between QTc and all-cause, cardiovascular, and ischemic heart disease mortality was studied in a population of 3,091 apparently healthy Dutch civil servants and their spouses, aged 40-65 years, who participated in a medical examination during 1953-1954. Moderate (QTc, 420-440 msec) and extensive (QTc, more than 440 msec) QTc prolongations significantly predict all-cause mortality during the first 15 years among men (adjusted respective relative risks [RRs], 1.5 and 1.7) and among women (RRs, 1.7 and 1.6). In men, cardiovascular (RRs, 1.6 and 1.8) and ischemic heart disease mortality (RRs, 1.8 and 2.1) mainly account for this association. In women, the association cannot be attributed specifically to cardiovascular and ischemic heart disease mortality. RRs for a subpopulation without any sign of heart disease at baseline are similar. The same is observed for QTc prolongation after light exercise, although in this situation most associations are not statistically significant, probably because of smaller numbers in the QTc prolongation categories.

CONCLUSIONS

Our results suggest that QTc contributes independently to cardiovascular risk. If autonomic imbalance is an important mechanism, it might be speculated that changes in life-style (e.g., with regard to physical exercise and smoking) may have a preventive impact.
Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade. A randomized, double-blind, placebo-controlled trial. Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study (CARPORT).
Authors: Serruys P W , Rutsch W , Heyndrickx G R , Danchin N , Mast E G , Wijns W , Rensing B J , Vos J , Stibbe J
Published: June 2012

BACKGROUND

GR32191B is a novel thromboxane A2-receptor antagonist with potent antiagregational and antivasoconstrictive properties. We have conducted a randomized, double-blind placebo-controlled trial to study its usefulness in restenosis prevention.

METHODS AND RESULTS

Patients received either GR32191B (80 mg orally before angioplasty and 80 mg/day orally for 6 months) or 250 mg i.v. aspirin before angioplasty and placebo for 6 months. Coronary angiograms before angioplasty, after angioplasty, and at 6-month follow-up were quantitatively analyzed. Angioplasty was attempted in 697 patients. For efficacy analysis, quantitative angiography at follow-up was available in 522 compliant patients (261 in each group). Baseline clinical and angiographic parameters did not differ between the two treatment groups. The mean difference in coronary diameter between postangioplasty and follow-up angiogram (primary end point) was -0.31 +/- 0.54 mm in the control group and -0.31 +/- 0.55 mm in the GR32191B group. Clinical events during 6-month follow-up, analyzed on intention-to-treat basis, were ranked according to the highest category on a scale ranging from death (control, six; GR32191B, four) to nonfatal infarction (control, 22; GR32191B, 18), bypass grafting (control, 19; GR32191B, 22) and repeat angioplasty (control, 52; GR32191B, 48). No significant difference in ranking was detected. Six months after angioplasty, 75% of patients in the GR32191B group and 72% of patients in the control group were symptom free.

CONCLUSIONS

Long-term thromboxane A2-receptor blockade with GR32191B does not prevent restenosis and does not favorably influence the clinical course after angioplasty.
Mitral regurgitation following mitral balloon valvotomy. Differing mechanisms for severe versus mild-to-moderate lesions.
Authors: Essop M R , Wisenbaugh T , Skoularigis J , Middlemost S , Sareli P
Published: June 2012

BACKGROUND

This study was designed to evaluate the incidence and mechanisms of mitral regurgitation following mitral balloon valvotomy (MBV) in 40 consecutive patients with symptomatic tight pliable mitral stenosis.

METHODS AND RESULTS

Transthoracic echocardiography with color flow mapping was performed before and 24 hours after the procedure. Patients who developed significant mitral regurgitation following MBV also underwent transesophageal echocardiography. The relation between increased mitral regurgitation and both valvular morphology and procedure-related factors was examined. Gorlin mitral valve area increased from 0.81 +/- 0.3 to 1.95 +/- 0.7 cm2 (p less than 0.001). No patient had more than 2+ mitral regurgitation by angiography and color Doppler prior to MBV. There was a moderate correlation between Doppler and angiographic increase in mitral regurgitation (r = 0.73, p less than 0.0001). By Doppler criteria 33 patients had no (n = 6) or mild (n = 27) increase in mitral regurgitation (group 1), and seven developed significant new mitral regurgitation (group 2). Baseline clinical, echocardiographic, and procedure-related data for the two groups were similar. Multiple regression analysis did not select any individual valve characteristic (valvular thickening, mobility, calcification, and subvalvular disease), total echocardiographic score, balloon diameter, or ratio of balloon to mitral annular diameter as disruption with a torn anterior or posterior mitral leaflet in six and a ruptured papillary muscle in one. Two of these patients have required mitral valve replacement (6 and 9 months following the procedure), whereas the remainder are significantly symptomatic. By contrast, mitral regurgitation in group 1 either occurred at the site of commissural split (n = 20) or was associated with prolapse of the anterior mitral leaflet (n = 6).

CONCLUSIONS

Thus, severe new mitral regurgitation following MBV is due to noncommissural tearing of the mitral leaflet and confers an adverse long-term prognosis. A mild increase in mitral regurgitation following MBV is frequent and occurs at the site of commissural split or is associated with prolapse of the anterior leaflet. Furthermore, in this study, an increase in mitral regurgitation could not be predicted from any valvular or procedure-related factor.
Induction of myocardial hypertrophy after coronary ligation in rats decreases ventricular dilatation and improves systolic function.
Authors: Litwin S E , Raya T E , Anderson P G , Litwin C M , Bressler R , Goldman S
Published: June 2012

BACKGROUND

Previous studies have shown that hypertrophy of surviving myocytes after myocardial infarction (MI) is limited. Progressive ventricular dilatation after MI may occur when compensatory hypertrophy cannot restore left ventricular (LV) wall stress to normal.

METHODS AND RESULTS

To test whether induction of additional myocyte hypertrophy might prevent pathological LV remodeling after large MI, we administered 2-tetradecylglycidic acid (TDGA) 20 mg/kg/day to sham-operated (n = 12) and MI (n = 10) rats for 10 days, beginning the third day after infarction. We have previously shown that chronic inhibition of long-chain fatty acid oxidation with TDGA in rats results in myocardial hypertrophy without any apparent impairment of LV systolic function. When compared with untreated MI rats (n = 9), we found that TDGA-treated MI rats had increases in LV weight/body wt, myocyte cross-sectional area, and peak developed LV pressure during abrupt aortic occlusion. MI rats treated with TDGA had lower LV end-diastolic pressures and smaller end-diastolic volumes, whereas stroke volume was maintained. The ex vivo passive LV pressure-volume relation was shifted toward the pressure axis compared with untreated infarct rats. In sham-operated rats, TDGA caused increases in LV weight/body wt, myocyte size, peak developed LV pressure, cardiac index, and stroke volume index, and a shift of the passive LV pressure-volume relation toward the pressure axis.

CONCLUSIONS

Induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of LV dilatation and produced beneficial effects on systolic function after large myocardial infarction. These data support the hypothesis that inadequate hypertrophy of residual myocardium after infarction may contribute to LV dilatation and the development of congestive heart failure.
Correlates of sodium-lithium countertransport. Findings from the Gubbio Epidemiological Study. The Gubbio Collaborative Study Group.
Authors: Trevisan M , Laurenzi M
Published: June 2012

BACKGROUND

Numerous reports have presented evidence for a positive association between the maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes and hypertension. The nature of this association remains to be clarified.

METHODS AND RESULTS

This report presents correlates of Na-Li CT in a population sample of 3,591 people aged 5-74 years. Males had higher mean age-specific levels of Na-Li CT than females except for the 5-14-year age stratum. In adults aged 25-74, for both men (n = 1,044) and women (n = 1,192), body mass index, plasma uric acid and glucose, alcohol consumption, and red blood cell mean corpuscular volume were positively related to countertransport in multivariate analyses; plasma high-density lipoprotein (HDL) cholesterol and plasma potassium were inversely related. Plasma non-HDL cholesterol was independently and directly related to Na-Li CT in women, and plasma sodium was inversely associated with Na-Li CT in men. These relations prevailed for men when persons with hypertension were excluded from the analyses and prevailed in part for women. When stepwise regression analyses were done for all men and women combined (n = 2,236), sex ceased to be significantly related to countertransport with plasma uric acid and alcohol intake in the model. In adults of either sex, no independent association was detected between Na-Li CT and age, heart rate, or the ratios of sodium to potassium or of sodium to creatinine in overnight untimed urine.

CONCLUSIONS

In both sexes, Na-Li CT is significantly and independently associated with a number of metabolic variables (plasma uric acid, plasma glucose, body mass index, plasma potassium, and life-style habits [e.g., alcohol intake]). Further research is needed to elucidate the meaning of the significant associations between Na-Li CT and the foregoing variables (all of them also related to blood pressure).
Short-term vasodilator effect of captopril in patients with severe mitral regurgitation is parasympathetically mediated.
Authors: Wisenbaugh T , Essop R , Sareli P
Published: June 2012

BACKGROUND

Few data exist regarding the effects of angiotensin converting enzyme inhibitors in patients with regurgitant valvular lesions. We postulated an immediate improvement in cardiac performance with captopril in mitral regurgitation, which, in a hemodynamically compensated group of patients, might be mediated through parasympathetic vasodilation rather than through blockade of angiotension converting enzyme.

METHODS AND RESULTS

Hemodynamics were examined before and 90 minutes after oral captopril (25-50 mg) in 18 patients (mean age, 31 years) with chronic, severe mitral regurgitation in New York Heart Association functional class II and III. One group of patients was given captopril alone (group 1, n = 9) and a second group was given captopril plus atropine 0.04 mg/kg i.v. (group 2, n = 9). Captopril alone (group 1) produced decreases in heart rate (90-81 beats/min, p less than 0.001), mean arterial pressure (90-73 mm Hg, p less than 0.001), systemic resistance (28-23 Wood units, p = 0.068), and pulmonary wedge pressure (19-14 mm Hg, p less than 0.001). There was no improvement in either arteriovenous oxygen difference or thermodilution cardiac output; in fact, the latter slightly declined (3.45-3.35 l/min, p = 0.002). Pretreatment with atropine (group 2) diminished the effects of captopril on heart rate (107-103 beats/min, p = 0.065 for atropine effect by two-way ANOVA), mean arterial pressure (88-82 mm Hg, p = 0.01 for atropine effect), and systemic resistance (26-27 Wood units, p = 0.04 for atropine effect).

CONCLUSIONS

In patients with chronic, severe mitral regurgitation, captopril reduced systemic arterial and left ventricular filling pressures but did not immediately augment cardiac output as expected. Furthermore, the modest systemic vasodilator effect of captopril was parasympathetically mediated.
Postischemic free radical production in the venous blood of the regionally ischemic swine heart. Effect of deferoxamine.
Authors: Mergner G W , Weglicki W B , Kramer J H
Published: June 2012

BACKGROUND

We tested the hypothesis that secondarily produced free radicals can be detected in venous coronary effluent without the need for direct exposure of postischemic tissue to the spin trapping agent alpha-phenyl-tert-butylnitrone (PBN).

METHODS AND RESULTS

The left anterior descending coronary artery (LAD) of pigs was ligated for 15, 30, 40, or 60 minutes, and the tissue was subsequently reperfused for 60 minutes. Venous effluent (6.5 ml) from the risk area was withdrawn sequentially at 1.5-minute intervals during reperfusion. The effluent blood was immediately infused (4.5 ml/min) with an isotonic saline solution containing 120 mM PBN: Preischemic control effluent samples were collected in an identical fashion. Plasma from each sample was extracted in organic solvent and subsequently analyzed by electron spin resonance (ESR) spectroscopy. Another group of pigs received an infusion of the metal chelator deferoxamine mesylate (25 mg/kg/hr) into the right atrium starting 1 hour before the 40-minute ligation and continuing throughout ligation and reperfusion. We were able to demonstrate the postischemic production of ESR signals for PBN adduct(s) from untreated hearts having spectral characteristics similar to an alkoxyl adduct (PBN-RO.; hyperfine splitting constants for beta-hydrogen [alpha H] = 2.0-2.25 G; nitrogen [alpha N] = 13.5-13.75 G). The reperfusion time course of PBN adduct production had a unique pattern: 1) multiple low-level bursts during the initial 15 minutes of reperfusion, and 2) a prominent PBN adduct signal during a relatively late time (20-25 minutes) of reperfusion. Total postischemic PBN adduct production rose with increasing duration (15-60 minutes) of ischemia and was associated with a progressive elevation of total lactate dehydrogenase in the effluent. Infusion of deferoxamine markedly diminished PBN adduct production as well as total release of lactate dehydrogenase.

CONCLUSIONS

These data suggest the potential feasibility of using an ex vivo ESR spin trapping technique in blood-perfused models of cardiovascular injury and that chelatable free iron contributes to the production of alkoxyl radicals.
Role of collagen in acute myocardial infarct expansion.
Authors: Whittaker P , Boughner D R , Kloner R A
Published: June 2012

BACKGROUND

We sought to determine if damage to the myocardial collagen network was the cause of infarct expansion.

METHODS AND RESULTS

Using polarized light microscopy, we examined sections from rat hearts obtained at 1, 2, 3, and 4 days after permanent coronary artery occlusion. Three features of the collagen network likely to be important in resisting infarct expansion were assessed: collagen quality, collagen quantity, and collagen organization. We observed a decrease in the number of normally birefringent collagen fibers in the infarct as early as 1 day after infarction. This decrease correlated significantly with time (r = -0.989, p less than 0.001). In addition, we found that the fewer normally birefringent collagen fibers present, the greater the degree of infarct expansion (assessed by measurement of total left ventricular cross-sectional area). At 4 days after infarction, we noted a loss of intermyocyte collagen struts and loss of interstitial space. These changes coincided with the onset of pronounced infarct expansion. The loss of collagen struts is consistent with the concept that expansion proceeds via slippage of myocytes previously tethered by the struts. The loss of interstitial space may represent the resolution of interstitial edema, which could further weaken the ventricular wall.

CONCLUSIONS

The correlation of infarct expansion with collagen damage and the loss of support provided by collagen struts suggest that collagen is important in maintaining structural integrity after acute myocardial infarction.
Double-transseptal, double-balloon valvuloplasty for congenital mitral stenosis.
Authors: Grifka R G , O'Laughlin M P , Nihill M R , Mullins C E
Published: June 2012

BACKGROUND

Eight patients with severe congenital mitral stenosis underwent double transseptal, double-balloon valvuloplasty; two had isolated congenital mitral stenosis, six had additional cardiac defects, and one had previous surgical valvotomy. Ages ranged from 0.6 to 36 years (median, 9 years).

METHODS AND RESULTS

All procedures were tolerated well. After valvuloplasty, the left atrial a wave minus the left ventricular end-diastolic pressure (LVEDP) gradient was reduced from 25 +/- 6 mm Hg to 9 +/- 3 mm Hg (p less than 0.001), the mitral valve mean gradient was reduced from 18 +/- 7 mm Hg to 8 +/- 3 mm Hg (p = 0.003), and the LVEDP was unchanged. All patients had marked clinical improvement. Only one patient developed significant mitral regurgitation. Two of the first four patients underwent repeat balloon valvuloplasty 7 months later. Follow-up evaluation on six patients from 4 to 54 months revealed no recurrence of symptoms or increased mitral regurgitation.

CONCLUSIONS

Double transseptal, double-balloon valvuloplasty is an effective treatment for many forms of congenital mitral stenosis. Mitral regurgitation is uncommon after this procedure. The double transseptal approach results in less trauma to the atrial septum and femoral veins and allows easy assessment of any residual postvalvuloplasty gradient.
Independent and incremental prognostic value of tests performed in hierarchical order to evaluate patients with suspected coronary artery disease. Validation of models based on these tests.
Authors: Pollock S G , Abbott R D , Boucher C A , Beller G A , Kaul S
Published: June 2012

BACKGROUND

The additive prognostic value of tests done in a hierarchical order for the detection of coronary artery disease (CAD) is not always known. The principal goal of this study, therefore, was to assess the incremental prognostic value of data obtained in succession (clinical, exercise stress testing, 201Tl imaging, and coronary angiography) in patients with suspected CAD. A second goal was to develop models for determining prognosis based on results of these tests and to test the clinical validity of these models in unrelated patients.

METHODS AND RESULTS

Data from two groups of patients who had undergone such evaluation and had been followed for a mean of 4.4 years were analyzed. There were 204 patients from Massachusetts General Hospital (MGH) and 299 from the University of Virginia (UVA). There were 20 deaths and 21 nonfatal infarctions in the MGH group and 41 deaths and nine infarctions in the UVA group. Both univariate and multivariate Cox regression analyses were performed to assess the individual and incremental prognostic value of these tests. In both groups, 201Tl imaging provided significant additional prognostic information compared with clinical and exercise stress test data (p less than 0.05). At MGH, where the lung/heart 201Tl ratio had been analyzed, coronary angiography did not provide additional prognostic information. In this group of patients, the combination of clinical and exercise 201Tl variables provided greater prognostic information than the combination of clinical and angiographic data (p less than 0.001). In the UVA cohort, in which the lung/heart ratio had not been analyzed, coronary angiography provided incremental prognostic information compared with clinical and exercise 201Tl data alone (p less than 0.05). When models developed using data from either sample were applied to the other unrelated sample, there was often close agreement between the overall observed rates and those predicted by the models. This was also true for the low-risk and high-risk subgroups. Some models, however, did not perform as well as other models, which suggests that models that do well in one sample may not always be generalized to other groups.

CONCLUSIONS

Tests performed in hierarchical order for the evaluation of suspected CAD provide additional prognostic information. Models developed using clinically relevant combinations of test results obtained from different patient populations are frequently able to predict absolute levels of survival in unrelated but similar samples.
Contractile properties and Ca2+ release activity of the sarcoplasmic reticulum in dilated cardiomyopathy.
Authors: D'Agnolo A , Luciani G B , Mazzucco A , Gallucci V , Salviati G
Published: June 2012

BACKGROUND

We performed a comparative study on Ca2+ release activity of the sarcoplasmic reticulum and calcium sensitivity of contractile apparatus of chemically skinned myocardial fibers obtained from four nonfailing human hearts and 13 excised hearts from patients with idiopathic dilated cardiomyopathy.

METHODS AND RESULTS

Ca2+ sensitivity of contractile apparatus was studied by following the isometric tension developed by chemically skinned myocardial fibers challenged with solutions of decreasing pCa. Ca2+ release from sarcoplasmic reticulum was monitored indirectly by measurement of the isometric tension developed by skinned fibers challenged with caffeine. We observed no significant difference of Ca2+ sensitivity and cooperativity between normal myocardium (pCa50 = 6.00 +/- 0.05; Hill coefficient, nHill = 2.07 +/- 0.10) and dilated cardiomyopathy (pCa50 = 6.03 +/- 0.07; nHill = 2.72 +/- 0.30) when the fibers were stretched to 130% of the resting length. We also found that both in normal myocardium and dilated cardiomyopathy, stretching to 150% of the resting length increased the Ca2+ sensitivity of the contractile system; pCa50 = 6.21 +/- 0.01 and 6.13 +/- 0.04 in normal and dilated cardiomyopathy, respectively, whereas in dilated cardiomyopathy there was a decrease of Hill coefficient with stretching that was not observed in the control group. The caffeine threshold in idiopathic dilated cardiomyopathy was markedly increased compared with the control group, 1.94 +/- 0.27 mmol/l and 0.29 +/- 0.04 mmol/l caffeine, respectively, whereas there were no significant differences in the extent and rate of caffeine-induced Ca2+ release.

CONCLUSIONS

These results indicate that in idiopathic dilated cardiomyopathy there is no alteration of contractile and regulatory proteins; on the contrary, the gating mechanism of the Ca2+ release channel of sarcoplasmic reticulum is abnormal, suggesting a possible involvement of the excitation-contraction coupling in the pathogenesis of this disease. It should also be taken into account, however, that the increased caffeine threshold in dilated cardiomyopathy would be a result of the enhanced resistance to the skinning procedure secondary to the modification of lipid species and/or content in sarcoplasmic reticulum membrane.
Importance of intraluminal pressure on hemodynamics and vasoconstriction responses of stenotic arteries.
Authors: Ghods M , Mangal R , Iskandrian A S , Santamore W P
Published: June 2012

BACKGROUND

Clinical and morphological studies clearly indicate that most human coronary artery stenoses are capable of vasomotion. Variable ischemic thresholds, ischemia unrelated to work load, and variant angina further show the presence and importance of vasoconstriction in coronary artery stenosis. Despite the importance of vasoconstriction, the effect of intraluminal pressure on the hemodynamic response to vasoconstrictors has not yet been examined. Intraluminal pressure is a primary determinant of vessel size and the force opposing vasoconstriction. Accordingly, we examined the effects of intraluminal pressure on the hemodynamic response to norepinephrine (NE)-induced vasoconstriction.

METHODS AND RESULTS

In canine carotid arteries perfused with physiological salt solution, pressures at the proximal and distal ends of the artery, as well as flow, were continuously recorded. We altered intraluminal pressure using three diverse interventions: changes in perfusion pressure, decreasing distal resistance, and collaterals. In normal, nonstenotic arteries, NE decreased the external vessel diameter but did not reduce flow. Perfusion pressure changes did not affect the ED50 of the NE-diameter relation. After an intraluminal stenosis was created, NE-induced constriction decreased flow. The threshold concentration of NE needed to decrease flow decreased as the perfusion pressure decreased (38.5 +/- 17.9, 2.3 +/- 1.3, and 0.12 +/- 0.1 x 10(-7) mol/l for 125, 100, and 75 mm Hg of perfusion pressure, respectively; p less than 0.05). Lowering distal resistance decreased stenotic pressure and decreased the threshold NE concentration from 5.4 +/- 1.9 to 0.34 +/- 0.2 x 10(-7) mol/l (p less than 0.05), and increasing stenotic pressure with collaterals increased the threshold NE concentration from 2.6 +/- 1.4 to 7.5 +/- 4.6 x 10(-7) mol/l (p less than 0.05).

CONCLUSIONS

In stenotic arteries, interventions that lowered the intraluminal pressure decreased the threshold NE concentration needed to decrease flow, and interventions that raised the intraluminal pressure increased the threshold NE concentration. This pressure-dependent constrictor sensitivity affects the vasomotor tone and is important in pathophysiology of ischemia occurring with hypotension (low perfusion pressure) or mild increase in myocardial oxygen demand (low distal arteriolar resistance). The results also suggest that collaterals, by maintaining stenotic pressure, could decrease the constrictor sensitivity and prevent ischemia.
Programmed electrical stimulation and drugs identify two subgroups of ventricular tachycardias occurring 16-24 hours after occlusion of the left anterior descending artery.
Authors: Vos M A , Gorgels A P , Leunissen J D , Havenith M G , Kriek E , Smeets J L , Wellens H J
Published: June 2012

BACKGROUND

Spontaneous sustained ventricular tachycardia (VT) occurring 16-24 hours after left anterior descending (LAD) coronary artery occlusion in the canine heart is most likely based on abnormal automaticity. In vitro, it has been demonstrated that the rate of the arrhythmia and the effect of overdrive pacing depends on the maximal diastolic potential (MDP). The MDP is also of importance in understanding the effect of antiarrhythmic drugs. To study 1) the possible presence of different responses to overdrive pacing and 2) the relation between the response to overdrive pacing and the effect of different antiarrhythmic drugs in the intact heart, we investigated the effect of 1) (prolonged) pacing and 2) lidocaine (3 mg/kg), verapamil (0.4-1.0 mg/kg), or flunarizine (2 mg/kg) during VT.

METHODS AND RESULTS

In 21 conscious dogs with chronic atrioventricular block, 60 sustained VTs were observed 1 day after LAD occlusion. During VT, pacing with interstimulus intervals of 400, 300, and 200 msec for 15, 60, and 120 seconds was done on 40 VTs. Based on their response to pacing, VTs were divided into a pacing-suppressible (PS group) and a pacing-nonsuppressible group (PNS group). The mean cycle length in the PS group was significantly longer (410 +/- 50 msec) than in the PNS group (360 +/- 35 msec, p less than or equal to 0.01). Suppression was directly related to the rate and duration of pacing. Spontaneous recurrence of VTs was observed after 26 +/- 45 seconds. Lidocaine and verapamil increased cycle length of the suppressible VTs and terminated them, whereas flunarizine had no effect. Except for verapamil, which increased cycle length of the VTs, no effects were seen in the PNS group.

CONCLUSIONS

In conscious dogs showing sustained VTs 16-24 hours after LAD occlusion, 1) the slower VTs can be suppressed by pacing, verapamil, and lidocaine but not by flunarizine, and 2) the faster VTs are not affected by pacing, lidocaine, and flunarizine, and are only slowed by verapamil. These findings are compatible with in vitro findings of abnormal automaticity, with the slower VTs originating from a higher MDP than the faster VTs.
Initial and long-term outcome of 354 patients after coronary balloon angioplasty of total coronary artery occlusions.
Authors: Bell M R , Berger P B , Bresnahan J F , Reeder G S , Bailey K R , Holmes D R
Published: June 2012

BACKGROUND

Coronary balloon angioplasty of chronic total occlusions is associated with relatively low success rates and a high incidence of restenosis. Whether there is long-term benefit in performing angioplasty of these lesions is unknown. The purpose of the present report was to analyze the long-term outcome of a large series of patients undergoing this procedure.

METHODS AND RESULTS

A computerized database analysis of 354 consecutive patients (from 1979 to 1990) who underwent coronary angioplasty of a chronic total coronary occlusion was performed (mean age, 62.3 years). Initial technical success was achieved in 69%; in 66%, success was achieved without procedural death or need for coronary artery surgery. During hospitalization, six patients suffered myocardial infarction, nine required emergency bypass surgery, and nine patients died. During a mean follow-up period of 2.7 years, no difference was found in survival or freedom from myocardial infarction among 234 successfully dilated patients compared with 120 patients with a failed attempt. However, the use of coronary artery bypass surgery was significantly less after successful dilation (p less than 0.0001 versus failed attempt). No significant difference in the cumulative incidence of severe angina was observed between these two patient populations, with the majority remaining asymptomatic. Restenosis occurred in 59% of 69 patients who returned for follow-up angiography.

CONCLUSIONS

Successful recanalization is achieved in the majority of patients undergoing angioplasty of chronic total occlusions and reduces the need for coronary artery bypass surgery. However, no major impact on either survival or incidence of myocardial infarction was noted after successful recanalization when patients with surgery were included.
Effects of lidocaine on relation between defibrillation threshold and upper limit of vulnerability in open-chest dogs.
Authors: Topham S L , Cha Y M , Peters B B , Chen P S
Published: June 2012

BACKGROUND

The purpose of the present study was to test the effects of lidocaine on the relation between the defibrillation threshold and the upper limit of vulnerability.

METHODS AND RESULTS

The shock strength associated with a 50% probability of successful defibrillation (DFT50) and the shock strength associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) were determined in 11 open-chest dogs by using the delayed up-down method before and during lidocaine (seven dogs) or normal saline (four dogs) infusion. The ventricles were paced at a cycle length of 300 msec. Shocks of various strengths were then given via a patch-patch electrode configuration on the anterior and posterior surfaces of the ventricle to determine the ULV50. Once ventricular fibrillation was induced, shocks were given 15-20 seconds later via the same electrode configuration to determine the DFT50. Lidocaine infusion resulted in a serum level of 15 +/- 4 micrograms/ml. This was associated with a lengthening of the QT interval but not with the widening of the QRS complex. In all dogs, both the ULV50 and the DFT50 increased significantly when tested during lidocaine infusion. Mean ULV50 during lidocaine infusion was 496 +/- 70 V or 13.1 +/- 4.3 J, which were significantly higher than the baseline values of 333 +/- 67 V or 5.3 +/- 2.2 J (p less than 0.001 for both voltage and energy). Mean DFT50 during lidocaine infusion was 407 +/- 41 V or 8.7 +/- 1.7 J, which were significantly higher than the baseline values of 300 +/- 38 V and 4.4 +/- 1.1 J (p = 0.004 for voltage and p = 0.013 for energy). The r values between the ULV50 and the DFT50 were 0.79 (p = 0.037) for voltage and 0.80 (p = 0.030) for energy at baseline and 0.85 (p = 0.016) for voltage and 0.88 (p = 0.009) for energy during the lidocaine infusion. However, the increments of the ULV50 (163 +/- 88 V or 7.8 +/- 4.6 J) were significantly greater than the increments of the DFT50 (107 +/- 51 V or 4.4 +/- 1.9 J, p = 0.035 for voltage and p = 0.023 for energy). Normal saline infusion did not alter DFT50 or ULV50.

CONCLUSIONS

Lidocaine infusion significantly increases both ULV50 and DFT50. These results are compatible with the upper limit of vulnerability hypothesis of defibrillation. However, the greater increase of the upper limit of vulnerability than the defibrillation threshold with lidocaine infusion indicates that other factors may also need to be considered to explain the results.