摘要:

BackgroundRecombinant DNA technologies have facilitated the development of a set of polymorphic DNA markers covering the human genome. General linkage analysis in families predisposed to inherited disease is now feasible. Linkage analysis can help identify a disease gene even when relatively little is known about the disorder.Methods and ResultsUsing this approach, we have identified linkage between a gene that causes the long QT syndrome and DNA markers on chromosome 11.ConclusionsThe identification of the chromosomal location of the long QT locus is the first step in defining the specific mutations that cause this disease.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundQuantitative coronary arteriography has been validated for stenotic segments of coronary arteries. However, it does not currently account for diffuse coronary artery disease, because the normal size of the coronary artery for its distal myocardial bed size is not known and cannot be measured directly with diffuse involvement of the artery.Methods and ResultsFrom clinical coronary arteriograms of 12 patients without coronary artery disease (group 1) and in 17 patients with coronary artery disease (group 2), we determined by quantitative coronary arteriography 1) the relations among measured coronary artery cross-sectional lumen area, summed distal branch lengths, and regional myocardial mass distal to each point in each coronary artery; 2) the ratio of coronary artery lumen area between parent and daughter vessels at 50 bifurcations; and 3) which of three different theoretical physical principles could underlie the tree structure of the human coronary artery system, by comparing the coronary artery size, branch lengths, regional mass, and relations between parent-to-daughter lumen area ratios with those for the different theoretical physical principles to test which principle best fit the observed data and therefore which principle most probably characterizes the human coronary artery tree structure. The results showed that 1) there is a close correlation between the lumen area of a coronary artery at each point along its length and the corresponding summed distal branch lengths and regional myocardial mass in patients without and with coronary artery disease; 2) measured coronary artery lumen area in patients with coronary artery disease is diffusely 30-50% too small for distal myocardial bed size compared with normal subjects; and 3) the observed relations among coronary artery size, distal summed lengths, myocardial bed size, and parent-to-daughter size ratios are not consistent with the theoretical principle of constant mean blood flow velocity in the coronary circulation but are consistent with the principles of minimum viscous energy loss and of limited/adaptive vascular wall shear stress characterized by a 2/3 power law relating coronary artery lumen area to distal summed branch lengths and regional mass or parent-to-daughter branching ratios.ConclusionsThese observations provide a basis for quantifying diffuse coronary artery disease on clinical arteriograms.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundIn humans, angiotensin converting enzyme (ACE) inhibition attenuates the vasoconstriction induced by sympathetic stimulation in a number of peripheral districts. Whether this is also the case in the coronary circulation is unknown, however.Methods and ResultsIn nine normotensive patients with angiographically assessed coronary atherosclerosis, we measured the changes in mean arterial pressure (intra-arterial catheter), heart rate, rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between mean arterial pressure and CBF) induced by the cold pressor test (CPT, 2 minutes) and diving (30 seconds), i.e., two stimuli eliciting a sympathetic coronary vasoconstriction. The measurements were performed in the control condition and 30 minutes after captopril 25 mg p.o. In the control condition, CPI caused an increase in mean arterial pressure and heart rate. Despite the increase in RPP (+20.7±3.2%,p<0.01), CBF did not change and CVR increased (+12.2±4.0%,p<0.05); diving caused an increase in mean arterial pressure and a reduction in heart rate. RPP increased (+14.3±3.5%,p<0.01), but despite this increase, there was a reduction in CBF and a marked increase in CVR (+37.3±7.4%,p<0.01). Captopril did not modify the blood pressure and heart rate responses to both stimuli except for a slight accentuation of the bradycardia to diving. Despite the unchanged or only slightly reduced RPP response, the increase in CVR was markedly and significantly attenuated (p<0.01).ConclusionsACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. This is probably due to removal of the facilitating influence of angiotensin II on sympathetic modulation of coronary vasomotor tone.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundIn response to the increasing use of percutaneous balloon mitral commissurotomy, the National Heart, Lung, and Blood Institute established the Balloon Valvuloplasty Registry in November 1987.Methods and ResultsBetween November 1, 1987, and October 31, 1989, 738 patients aged 18 or older underwent percutaneous balloon mitral commissurotomy at the clinical sites. Data were prospectively entered into the registry at the time consent was obtained. Serious complications occurred in 87 procedures, or 12%. Death in the laboratory occurred in eight patients, or 1%. Within 30 days there were 24 cumulative deaths, 18 cardiac and six noncardiac. Univariate analysis revealed that older age, a history of cardiac arrest, cerebrovascular disease, dementia, renal insufficiency, cachexia, class IV congestive heart failure, use of an intra-aortic balloon pump, use of sympathomimetic amines, and a high echo score (≥13) were associated with early death (p<0.01). Additional univariate predictors included a precommissurotomy mitral valve area of <0.7 cm2. Left atrial pressure >12 mm Hg and a mitral valve area of <1.5 cm2after the procedure were also associated with higher 30-day mortality (p<0.05). Multivariate analysis identified higher echo score and smaller valve area before the procedure as the strongest predictors of early death (p<0.001). Centers that performed more than 25 procedures also had lower complication rates.ConclusionsAlthough percutaneous balloon mitral commissurotomy appears to be effective at relieving the hemodynamic effects of rheumatic mitral stenosis, it does have risks. In properly selected patients, however, it appears to have low morbidity and 30-day mortality. Individual center experience with the procedure also appears to have great impact on complications.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundGenetic lipoprotein disorders have been associated with premature coronary artery disease (CAD).Methods and ResultsThe prevalence of such disorders was determined in 102 kindreds (n=603 subjects) in whom the proband had significant CAD documented by angiography before the age of 60 years. Fasting plasma cholesterol, triglyceride, low density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and lipoprotein (a) [Lp(a)] values above the 90th percentile and high density lipoprotein (HDL) cholesterol and apo A-I below the 10th percentile of age- and sex-specific norms were defined as abnormal. An abnormality was noted in 73.5% of probands compared with 38.2% in age-matched controls (p<0.001), with a low HDL cholesterol level (hypoalphalipoproteinemia) being the most common abnormality (39.2% of cases). In these kindreds, 54% had a defined phenotypic familial lipoprotein or apolipoprotein disorder. The following frequencies were observed: Lp(a) excess, 18.6% (includes 12.7% with no other dyslipidemias); hypertriglyceridemia with hypoalphalipoproteinemia, 14.7%; combined hyperlipidemia, 13.7% (11.7% with and 2.0% without hypoalphalipoproteinemia); hyperapobetalipoproteinemia (elevated apo B only), 5%; hypoalphalipoproteinemia, 4%; hypercholesterolemia (elevated LDL only), 3%; hypertriglyceridemia, 1%; decreased apo A-I only, 1%. Overall, 54% of the probands had a familial dyslipidemia; unclassifiable lipid disorders (spouse also affected) were found in 3%. No identifiable familial dyslipidemia was noted in 43% of kindreds of those; nearly half (45%) had a sporadic lipid disorder. Parent-offspring and proband-spouse correlations for these biochemical variables revealed that lipoprotein and apolipoprotein levels are in part genetically determined, with Lp(a) showing the highest degree of parent-offspring correlation.ConclusionsOur data indicate that more than half of patients with premature CAD have a familial lipoprotein disorder, with Lp(a) excess, hypertriglyceridemia with hypoalphalipoproteinemia, and combined hyperlipidemia with hypoalphalipoproteinemia being the most common abnormalities.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundLipoprotein(a) [Lp(a)] is a low density lipoprotein-like particle whose apolipoprotein B (apo B) moiety is disulfide-linked to apo(a), a plasminogen-like inhibitor of fibrinolysis in vitro. We hypothesized that plasma concentrations of Lp(a) are acutely affected by intravenous tissue-type plasminogen activator (t-PA).Methods and ResultsPatients with unstable angina were randomized to receive either intravenous t-PA (n= 15) or placebo (n=11). Two-way ANOVA using repeated measures revealed a significant effect of t-PA on concentrations of Lp(a) (p=0.026). There was a 48% fall in Lp(a) from baseline concentrations in the t-PA group at 12 hours (p=0.031) but not at 72 hours. Lp(a) in the placebo group was unchanged.ConclusionsWe conclude that t-PA produces a sharp and substantial but reversible reduction in plasma Lp(a). These data suggest that Lp(a) concentration is not as static in vivo as had been believed and might be acutely modifiable through some mechanism that induces its removal from the freely circulating state.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundElevated levels of cholesterol and apoprotein B (apo B), the essential carrier protein for low density lipoprotein, are major lipid risk factors for premature coronary disease. Antiarrhythmic agents are frequently prescribed to patients with coronary heart disease and associated cardiac arrhythmias. As part of another study, we retrospectively investigated the effect of antiarrhythmic agents on blood lipids.Methods and ResultsThe study population consisted of 1,567 postinfarction patients on whom we prospectively collected serial blood samples for lipid and apoprotein determinations and recorded the concomitant medications the patients were receiving at three follow-up time periods. The lipids, analyzed at a central core laboratory, included total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL C), and apoproteins A-I (apo A-I), A-II (apo A-lI), and apo B. The difference in the group mean lipid values for patients receiving and not receiving type Ia antiarrhythmic agents (quinidine, procainamide, and disopyramide) was evaluated by the two-sample t test, and multiple linear regression analyses were performed to adjust for relevant covariates. Patients using type Ia antiarrhythmic agents at the 30-month postinfarction contact (n=76) had 8.6% lower cholesterol (p<0.003), 22.3% lower triglycerides (p<0.0002), 6.2% lower apo A-I (p=0.02), 10.1% lower apo A-II (p<0.001), and 12.7% lower apo B (p<0.000l) levels than patients not on these medications (n=1,491). These lower lipid levels were found after adjustment for age, sex, diabetes, smoking status, concomitant medications, and a variety of clinical factors relating to the severity of the coronary disease process. The HDL C levels were similar in those receiving and not receiving type Ia agents.ConclusionsPatients on type Ia antiarrhythmic agents had significantly and meaningfully lower cholesterol, triglyceride, apo A-II, and apo B levels than patients not receiving these agents. The mechanism of this hypolipidemic effect is undefined, but the mechanism may be related to an alteration by these agents of ionic membrane currents at the hepatocyte level.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundPrior research has suggested a weaker parasympathetic antagonism of sympathetic effects on the heart in type A (coronary-prone) men. To confirm this phenomenon and extend our understanding of it, we investigated the effects of prior muscarinic blockade on the electrocardiogram T wave and other cardiovascular and neuroendocrine responses to isoproterenol in type A and type B (non-coronary-prone) men.Methods and ResultsResponses to two 5-minute intravenous isoproterenol infusions (0.01 μg/kg/min and 0.02 Xμg/kg/min) were evaluated in six type A and six type B men after pretreatment with either dextrose placebo or atropine (1.2 mg). Atropine significantly potentiated T wave attenuation in the recovery period after isoproterenol infusion (0.30±0.07 mV) compared with placebo (0.54±0.09 mV,p<0.00l). Atropine also potentiated the heart rate increase to isoproterenol (39±3 beats per minute versus 20±2 beats per minute after placebo). Atropine enhanced decreases in systolic, diastolic, and mean arterial pressures as well as pulse pressure to isoproterenol. Atropine enhancement of many of these responses was increased among subjects with high scores on various hostility/anger scales. Isoproterenol alone produced greater T wave attenuation in type A than in type B men. However, atropine enhancement of T wave attenuation and blood pressure falls by isoproterenol was present only in type B men.ConclusionsThese findings indicate that there is accentuated parasympathetic antagonism of T wave attenuation and blood pressure responses induced by β-adrenergic stimulation. Relative weakness of this antagonism of sympathetic effects on the heart in hostile type A individuals may contribute to their higher coronary disease risk.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundThe signal-averaged ECG has been used to detect late potentials, and it is considered a noninvasive marker for areas of slow conduction requisite for reentrant arrhythmia. Late potentials are not usually found in patients with idiopathic ventricular tachycardia (VT); nevertheless, fragmented electrograms are often recorded in those patients during endocardial mapping. The purpose of this study was to investigate the spectral content of the signal-averaged ECGs with use of fast Fourier transform analysis (FFT) in patients with idiopathic VT of left ventricular origin.Methods and ResultsSignal-averaged ECGs were recorded in 12 patients with idiopathic VT originating from the left ventricle (group 1) and 25 age-matched normal volunteers (group 2). Frequency analysis with FFT1 was performed with a Blackman-Harris window in a segment length of 120 msec from 40 msec before the end of the QRS complex, and the frequency spectrum was displayed in a three-dimensional graph. Area ratio 1 (area of 20–50 Hz/area of 10–50 Hz) and area ratio 2 (area of 40–100 Hz/area of 0–40 Hz) were calculated in all subjects. Late potentials defined by the time domain were negative in all subjects. The area ratios of group 1 were significantly higher than those of group 2. High-frequency components in the three-dimensional graph were confined within the QRS complex.ConclusionsThese results suggest that frequency analysis of signal-averaged ECGs with FFT is an available method for detecting the high-frequency component within the QRS complex in some patients with idiopathic VT of left ventricular origin.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

BackgroundThere were few studies on the relation between the body surface distribution of high- and low-frequency components within the QRS complex and ventricular tachycardia (VT).Methods and ResultsEighty-seven signal-averaged ECGs were obtained from 30 normal subjects (N group) and 30 patients with previous anterior myocardial infarction (MI) with VT (MI-VT[+] group,n=10) or without VT (MI-VT[−] group,n=20). The onset and offset of the QRS complex were determined from 87-lead root mean square values computed from the averaged (but not filtered) ECG waveforms. Fast Fourier transform analysis was performed on signal-averaged ECG. The resulting Fourier coefficients were attenuated by use of the transfer function, and then inverse transform was done with five frequency ranges (0–25, 25–40, 40–80, 80–150, and 150–250 Hz). From the QRS onset to the QRS offset, the time integration of the absolute value of reconstructed waveforms was calculated for each of the five frequency ranges. The body surface distributions of these areas were expressed as QRS area maps. The maximal values of QRS area maps were compared among the three groups. In the frequency ranges of 0–25 and 150–250 Hz, there were no significant differences in the maximal values among these three groups. Both MI groups had significantly smaller maximal values of QRS area maps in the frequency ranges of 25–40 and 40–80 Hz compared with the N group. The MI-VT(+) group had significantly smaller maximal values in the frequency ranges of 40–80 and 80–150 Hz than the MI-VT(−) group. These three groups were clearly differentiated by the maximal values of the 40–80–Hz QRS area map.ConclusionsIt was suggested that the maximal value of the 40–80-Hz QRS area map was a new marker for VT after anterior MI.

ISSN:0009-7322    

出版商:OVID    

年代:1992

数据来源: OVID