摘要:

Background The objective of this study was to evaluate different tests of heart viability in a pig model of warm ischemia.Methods and Results Pig hearts (n=30) were submitted to 0 (= group I), 10 (group II), 20 (group III), 30 (group IV), and 60 (group V) minutes of in situ warm ischemia (animal exsanguination). Hearts were removed, then flushed with cardioplegic solution for 3 minutes at a fixed pressure of 60 cm H2O, and edema formation, initial coronary flow, and ionic composition (Na sup +, K sup +, and Ca sup ++) of coronary sinus effluent were evaluated. Hearts were then stored for 2 hours in a cold (4 degrees C) preservation solution. Myocardial biopsies (and evaluation of energetic index) were performed, then the hearts were reperfused for 30 minutes with whole blood with an in vitro functional testing system. No edema occurred during cardioplegic flush in the hearts in groups I through IV, but a 37+-11% weight increase (P<.001) occurred in hearts in group V. There was a progressive decrease in initial coronary flow with the increase in the duration of warm ischemia (70+-14 mL/min per 100 g of tissue in group I and 52+-9, 41+-16, 25+-11, and 23+-5 mL/min per 100 g, respectively, in groups II through V (P<.01 to P<.001 versus group I). Initial coronary flow was positively correlated with the energetic index (r=.84, P<.001), and the left ventricle developed pressure at reperfusion (r=.90, P<.001). Finally, there were significant differences between hearts in the control group and those in group V for calcium and sodium release (lower in the control group; P<.001 and P<.01, respectively) and for potassium removal (lower in group V, P<.05).Conclusions These data suggest that early measurement of coronary flow after removal of the heart may help to assess heart viability before transplantation. This approach may provide a comprehensive clinical evaluation to increase the number of hearts available for transplantation among those that are rejected in the absence of accurate criteria of viability. (Circulation. 1995;91:257-261.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Catecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic beta -adrenergic blocking property of dl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties of dl-sotalol with those of d-sotalol, which is devoid of significant beta -adrenergic blocking effect, before and after isoproterenol infusion.Methods and Results Action potential duration at 90% repolarization (APD sub 90) was prolonged in isolated guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10 sup -4 mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90for d-sotalol and dl-sotalol over control were 10.9+-2.5 to 23.7+-4.8 ms and 27.9+-4.0 to 39.0+-5.6 ms, respectively. APD90shortened to less than control in papillary muscles treated with d-sotalol but not dl-sotalol on addition of isoproterenol 10 sup -6 mol/L: -31.2+-3.5 to -18.3+-4.8 ms and 10.5+-3.6 to 33.3+-7.8 ms, respectively, P<.003. Single guinea pig ventricular myocytes were studied by the whole-cell patch clamp method. Time-dependent (Iout) and total (Itot) outward current in response to a 300-ms pulse to 20 mV and tail current (Itail) to -35 mV were measured after Ca2+ channel block and Na sup + channel inactivation. Iout, Itail, and Itotwere reduced in myocytes perfused with d-sotalol and dl-sotalol 10 sup -4 mol/L: Iout, -36.1+-4.1%, -40.5+-3.3%; Itail, -59.3+-4.6%, -62.2+-11.1%; Itot, -27.3+-4.3%, -50.0+-11.8%. Ioutand Itotincreased to a greater degree in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol 10 sup -6 mol/L: Iout, 100.3+-20.6%, 11.3+-7.6%, P=.002; Itot, 86.8+-39.2%, -41.1+-20.9%, P=.01. Itailtended to increase more in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol, but the difference was not significant (-9.1+-13.5%, -28.0+-9.0%).Conclusions The beta -adrenergic blocking property of dl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy of dl-sotalol in diminishing ventricular arrhythmia recurrence. (Circulation. 1995; 91:262-264.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background There is ample evidence from cross-sectional studies of an association between allelic variation of the gene coding for apolipoprotein E (apoE) and interindividual variation in plasma lipids, and the presence of coronary heart disease (CHD). There have been no prospective studies, however, to evaluate the usefulness of allelic variation of the apoE gene for predicting CHD.Methods and Results Two samples of elderly Finnish men were followed for 5 years, one in the east (n=297) and the other in the southwest of Finland (n=369). At baseline, when the apoE genotypes were assessed, the men were 65 to 84 years old. At the end of the follow-up, the vital status of each man was determined, and cause of death was coded. At baseline, relative frequencies of the three alleles- epsilon 2, epsilon 3, and epsilon 4-were 0.037, 0.827, and 0.136 in the eastern and 0.062, 0.763, and 0.175 in the southwestern samples, respectively (chi squared (chi2) =8.89, df=2, P<.012 for difference between the samples). During the 5-year follow-up, a total of 28 deaths from CHD were recorded in the eastern and 42 in the southwestern sample. Relative CHD mortality was not heterogeneous between the samples. Among those who died from CHD, there was a doubling of the relative epsilon 4 allele frequency in both samples (chi squared (chi2) =4.70, df=1, P<.03 for the eastern sample; chi squared (chi2) =7.11, df=1, P<.01 for the southwestern sample).Conclusions Allelic variation in the apoE gene is a statistically significant predictor of CHD death in these samples of elderly Finnish men. (Circulation. 1995;91:265-269.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background We analyzed an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene in 1226 subjects from the Caerphilly Prospective Heart Disease Study. Amplification of genomic DNA using the polymerase chain reaction yielded the genotypes II, ID, and DD. Distribution of the polymorphism was analyzed among the whole group and within subgroups (specified following multiple risk factor analysis) for coronary artery disease (CAD) and against multiple risk factors.=140/90 or on hypotensive medications, the DD genotype still associated with CAD (P<.07, n=210, TC/HDL <5.654 and P<.016, n=135, TC/HDL <5.0). Further stratification of risk incorporating other risk factors, except body mass index, did not alter or enhance this association. Although similar association was observed when risk was specified by using HDL and apo B levels instead of TC/HDL, this association was lost when body mass index was included in the low-risk stratification.Conclusions The DD genotype is a linkage marker for an etiologic mutation at or near the ACE gene that may confer risk of CAD detectable in subjects previously unidentifiable with "classic" risk factors. However, this risk may be quantitatively small among the general male population. (Circulation. 1995;91:270-274.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background The atrial appendage is a predilection site for thrombus formation. Mast cells (MC) are a rich source of mediators that may be involved in the regulation of thrombus formation. We examined number, distribution, and phenotype of MC in thrombosed versus unaffected auricles to elucidate their possible role in auricular thrombosis (AUTHR).Methods and Results Sections of atrial appendages (AUTHR, n=14; controls (CO), n=13) were analyzed for MC by Giemsa, toluidine blue, and berberine sulfate stains and by immunohistochemistry. Cardiac MC expressed CD antigens corresponding to the classic MC phenotype as well as tryptase, chymase, and heparin. Thrombosis was associated with a twofold increase in the number of MC in the total appendage (CO, 3.1+-1.0 versus AUTHR, 6.4+-1.1 MC/mm2, P<.01). Moreover, in AUTHR, a redistribution of MC to the upper endocardium was observed (AUTHR, 5.3+-1.4 versus CO, 0.07+-0.15 MC/mm2, P<.01). Mast cell growth factor (MGF) was expressed in the endothelium and subendothelial space of thrombosed appendages but not in the normal endocardium. Overexpression of MGF was accompanied by a weak or absent expression of the MGF receptor c-kit on redistributed MC in AUTHR. Patients with unilateral atrial appendage thrombosis did not exhibit a MC increase or redistribution in the unaffected contralateral appendage. No augmentation of other inflammatory cells was observed. Stimulation of isolated cardiac MC with MGF resulted in mediator release.Conclusions This study provides evidence that AUTHR is associated with MC increase and redistribution and MGF overexpression. The role of redistributed MC and their mediators in the pathophysiology of atrial thrombosis requires further investigation. (Circulation. 1995;91:275-283.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Thrombosis, provoked by a rupture of an atherosclerotic plaque, plays a crucial role in precipitating a coronary heart disease event. Its role at the early stage of atherosclerosis has, however, been unclear, but it has been hypothesized that thrombosis or defective fibrinolysis contributes to the progression of atherosclerotic lesions.Methods and Results We studied the association of plasminogen activator inhibitor antigen (PAI-1), tissue-type plasminogen activator antigen (TPA), and D-dimer with early atherosclerosis in a cross-sectional case-control study involving 457 pairs chosen from the biracial cohort of the Atherosclerosis Risk in Communities (ARIC) Study. As examined by B-mode ultrasound, patients (cases) had intima-media thickness of carotid arteries above the 90th percentile and control subjects had thickness below the 75th percentile of the ARIC cohort. Persons with a history of heart disease, stroke, or claudication were excluded from the case-control selection. PAI-1, TPA, and D-dimer were higher in patients than in control subjects (P<=.001, Wilcoxon signed rank statistic). In conditional logistic regression analyses, the odds ratios of carotid atherosclerosis were, for PAI-1, for example, 1.22, 1.54, and 1.60 in the second, third, and fourth quartiles compared with the first quartile (P<.0001, test of linear trend, adjusting for age, systolic blood pressure, total cholesterol, acetylsalicylic acid use, and time of blood draw). Corresponding tests for D-dimer and TPA also showed an increasing trend (P<.0001).Conclusions The findings support the hypothesis that thrombosis and fibrinolysis play a role at the early stage of the atherosclerotic process. (Circulation. 1995;91:284-290.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background In the experimental setting, it has been demonstrated that preconditioning myocardium before prolonged occlusion with brief ischemic episodes affords substantial protection to the cells by delaying lethal injury, thereby limiting infarct size. Whether the same occurs in humans remains unknown.50%), (3) a patent infarct-related coronary artery with TIMI 3 flow and complete absence of collateral circulation to the infarct related artery (assessed at 24+-5 days), and (4) the presence of new-onset prodromal angina, ie, typical chest pain episodes occurring at rest within 24 hours or, alternatively, a complete absence of symptoms before onset of infarction. Therefore, on the basis of their clinical status before infarction, the patients were divided into two groups: group 1, 13 patients without prodromal angina, and group 2, 12 patients with prodromal angina. Despite no difference in time to treatment (81+-19 versus 75+-21 minutes in group 1 and group 2, respectively; P=NS) and time to reperfusion (58+-34 versus 46+-24 minutes; P=NS), the peak of CKMB release was markedly lower in group 2 (86.3+-66 versus 192.3+-108.3 IU/L; P<.01). In addition, although both groups were comparable in terms of area at risk (amount of myocardium beyond the infarct-related stenosis; 15.1+-4.6 versus 13.7+-4.6 hypokinetic segments in group 1 and group 2, respectively, P=NS), the final infarct size (11+-7.5 versus 5.6+-4 hypokinetic segments, P<.04) was smaller in group 2. Thus, the limitation of the infarct size was significantly greater in group 2 (69% versus 36%; P<.05), and this represents an additional 33% reduction (95% confidence intervals, 7.1% to 58.9%; P=.01) in the group of patients with prodromal angina. Also, the third index, that is, the ECG, showed a favorable trend toward a lesser number of Q waves and a higher Sigma R waves, although the values did not reach statistical significance.Conclusions Despite a similar area at risk, patients with new-onset prodromal angina showed a significantly smaller infarct size compared with patients without prodromal symptoms. Since the two groups had similar times to reperfusion and no evidence of collateral circulation to the infarct related artery, the protection afforded by angina in group 2 patients might be explained by the occurrence of ischemic preconditioning. (Circulation. 1995;91:291-297.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Smoking is known to be a strong risk factor for premature atherosclerosis, myocardial infarction, and sudden cardiac death. Unexpectedly, in the reperfusion era, investigators have reported that patients who smoke have a more favorable prognosis after thrombolysis compared with nonsmokers. Since smoking is associated with a relatively hypercoagulable state, we hypothesized that the coronary occlusion responsible for infarction may be primarily thrombotic, with improved outcome relating to enhanced patency or the absence of a residual stenosis after thrombolytic therapy.Methods and Results To examine this issue, we evaluated 1619 patients treated with TPA, urokinase, or both in six consecutive myocardial infarction trials, of whom 878 (54%) were currently smoking. Patients underwent 90-minute and predischarge catheterizations, which were quantified blinded to the patients' smoking status. As expected, baseline fibrinogen (2.8 M(2.5, 3.6) versus 2.7 (2.4, 3.5) g/dL, P=.003) and hematocrit (44% (41%, 47%) versus 43% (40%, 45%), P=.0001) levels were greater in smokers. Although there were no differences between smokers and nonsmokers with regard to 90-minute patency (73% versus 74%), smokers were more likely to have TIMI-3 flow (41.1% versus 34.6%, P=.034), with a larger minimum lumen diameter of the infarct stenosis both acutely (0.82 (0.51, 1.11) versus 0.72 (0.43, 1.04) mm, P=.0432) and at follow-up (1.2 (0.8, 1.74 ) versus 1.0 (0.7, 1.5), P=.002). Although smokers tended to have reduced in-hospital mortality compared with nonsmokers in univariate analysis (4.0% versus 8.9%, P=.0001), after adjustment for baseline differences between smokers and nonsmokers in age (54 (47, 62) versus 60 (54, 68) years, P<.0001), inferior infarct location (60% versus 53%, P<.0001), three-vessel disease (16% versus 22%, P<.001), and baseline ejection fraction (53% (44%, 60%) versus 50% (42%, 58%), P=.0069), smoking history was of no independent prognostic significance.Conclusions Therefore, smokers have a relatively hypercoagulable state, documented by increased hematocrit and fibrinogen levels. Quantitative coronary angiographic analysis suggests that the mechanism of infarction in smokers is more often thrombosis of a less critical atherosclerotic lesion compared with nonsmokers. Enhanced perfusion status, as well as favorable baseline clinical and angiographic characteristics, may be responsible for the more benign prognosis of current smokers. (Circulation. 1995;91:298-303.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Because left ventricular (LV) diastolic function is impaired before systolic function in patients with ischemic heart disease and because ischemic heart disease is constituted of regional rather than global abnormalities of the left ventricle, measures of LV regional diastolic dysfunction, if possible, should provide the most sensitive assessment of the coronary involved region. The objectives of this study are to clarify whether high-frame-rate two-dimensional echocardiography, combined with digital subtraction image processing, may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease and to clarify whether this technique provides a measure for the noninvasive assessment of the coronary involved region.Method and Results In 30 normal subjects and 59 patients with ischemic heart disease, two-dimensional echocardiograms obtained at a rate of 60 frames per second were provided on line for digital subtraction analysis, with which digitized images were continuously subtracted on a frame-by-frame basis. The subtracted images were analyzed to determine the onset of the segmental outward motion of the LV wall in early diastole in each of 16 segments per subject. Regional relaxation index, defined as the interval from the second heart sound to the onset of outward wall motion, was significantly prolonged in the coronary involved segments compared with the normal segments (36.3+-18.0 versus 101.2+-34.0 ms, P<.01). The prolongation in the regional relaxation index was observed even in the coronary involved segments without reduction in systolic wall motion. When a cutoff level of 50.0 ms was used, coronary involved segments could be distinguished from normal or border segments with a sensitivity of 92% and a specificity of 81%.Conclusions Digital subtraction high-frame-rate echocardiography may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease. The time interval from the second heart sound to the onset of the segmental outward motion of the LV wall (regional relaxation index) obtained with this technique provides a noninvasive and accurate measure for assessing coronary involved regions. (Circulation. 1995;91:304-312.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Our objective was to compare the sensitivity and specificity of tetrofosmin, a new Technetium-99m-labeled myocardial perfusion imaging agent for the detection of myocardial perfusion abnormalities, with those of Thallium-201 and coronary angiography. Our hypothesis was that same-day stress/rest tetrofosmin imaging could provide data comparable to those of Thallium-201 imaging. Myocardial perfusion imaging plays an important role for the evaluation of coronary artery disease. Newer Technetium-99m-labeled agents offer several advantages over Thallium-201, the conventional myocardial perfusion imaging agent. Tetrofosmin is a new Technetium-99m-labeled agent with promising results in preliminary studies.Methods and Results Two hundred fifty-two patients with suspected coronary artery disease were enrolled in 10 centers in the United States and Europe. All patients underwent exercise and rest myocardial perfusion imaging with Technetium-99m-tetrofosmin using two separate injections of the radiotracer 4 hours apart on the same day. Planar images were obtained in three standard views 15 to 60 minutes after radiotracer injection. Patients also underwent standard exercise and redistribution planar Thallium-201 imaging within 2 weeks of tetrofosmin imaging. In addition, 58 healthy subjects with low likelihood of coronary artery disease underwent exercise and rest tetrofosmin imaging. Coronary angiograms were available in 181 patients with suspected coronary artery disease. All radionuclide images were processed in the central core laboratory and interpreted blindly by a panel of four experienced readers. Thallium-201 images and tetrofosmin images were read separately. Discrepancies were resolved by consensus. The workload, peak heart rate, and double products were comparable during exercise for both imaging agents. Technically acceptable paired Thallium-201 and tetrofosmin images were available in 224 of 252 patients. Tetrofosmin images were generally of good quality, with low extracardiac activity, and easy to interpret. Patients were categorized as showing normal, ischemia, infarction, or mixture with each imaging modality. Precise concordance for each of these categories was 59.4% (kappa =0.44; 95% CI, 0.35 to 0.53). When patients were categorized as normal or abnormal, the concordance was 80.4% (kappa =0.55; 95% CI, 0.43 to 0.67). When each of five anatomic territories (septal, anterior, inferior, lateral, and apical) was categorized as normal versus abnormal, the concordance varied from 81% to 90%. When similar comparison was made for the specific category of abnormality, the concordance was 64% to 84%. When coronary angiography was used as the criterion, the sensitivity and positive and negative predictive accuracy of tetrofosmin and Thallium-201 were comparable. The normalcy rate of tetrofosmin images in the healthy subjects with low likelihood of coronary artery disease was 97%.Conclusions Technetium-99m tetrofosmin is a new myocardial imaging agent with favorable imaging characteristics with results comparable to those of Thallium-201. (Circulation. 1995;91:313-319.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID