摘要:

BackgroundSeveral angiotensin-converting enzyme inhibitors have antiproliferative effects in a rat model after carotid artery balloon injury.Methods and ResultsWe conducted a randomized, doubleblind, placebo-controlled trial to assess the effect of fosinopril, novel angiotensin-converting enzyme inhibitor, in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received fosinopril or matched placebo 10 mg at least 18 hours before PTCA, 20 mg at least 4 hours before PTCA, and 40 mg daily for 6 months. In addition, patients received aspirin. Coronary angiograms before PTCA and immediately after PTCA as well as at 6-month follow-up were quantitatively analyzed. A total of 509 patients were recruited. The final per-protocol population consisted of fosinopril-treated and 151 placebo-treated patients. Restenosis rates according to the National Heart, Lung, and Blood Institute criterion 4 (loss of ≥50% of the initial gain primary end point]) were 45.7% and 40.7% in the fosinopril and control groups, respectively (not significant). The respective mean differences in minimal coronary luminal diameter between post-PTCA and follow-up angiograms were −0.59±0.71 mm and −0.51±0.67 mm (not significant). Clinical events during the 6-month follow-up period, analyzed on an on-treatment basis, were ranked according to the most serious event. The respective numbers in the fosinopril and the control groups were for death, 0 and 0; myocardial infarction, and 0; coronary artery bypass graft surgery, 1 and 3; repeat PTCA, 35 and 35; recurrent signs of ischemia necessitating early repeat coronary angiography and managed medically, 6 and 7; and none of the above, 111 and 106. All these differences were insignificant.ConclusionsConclusions Administration of fosinopril in a dose of 40mg daily during 6 months after PTCA does not prevent restenosis and has no effect on overall clinical outcome.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundEndothelial dysfunction and abnormal vascular responsiveness to vasoconstrictors may play an important role in chronic heart failure (CHF). The purpose of our study was to (1) evaluate whether the vascular response to norepinephrine is abnormal in a rat model of heart failure; (2) investigate the role of α1- and α2-adrenergic receptors; and (3) assess the contribution of the endothelium, and specifically endothelium-derived nitric oxide, to this response.Methods and ResultsConcentration-response curves of rat thoracic aortic rings were studied in isolated organ baths at 1 week after coronary artery ligation. In CHF rats, norepinephrine- induced contractions were increased in intact rings compared with rings from sham rats, despite decreased contraction in denuded rings. Decreased α1-receptor sensitivity was demonstrated by the increased EC50of methoxamine in endotheliumdenuded rings from CHF rats, although maximal responses to KCl contraction were also decreased in CHF. There was no difference in the vascular response to clonidine, and acetylcholine- mediated relaxations were preserved in CHF rats, suggesting normal stimulated nitric oxide release. However, nitric oxide synthase inhibition with Nω-nitro-L-arginine methyl ester, as well as measurements of basal cGMP, demonstrated that basal nitric oxide release was decreased in CHF rats.ConclusionsThis study demonstrates that the increased vascular responsiveness to norepinephrine in intact vessels from rats with heart failure is the result of decreased basal nitric oxide release and suggests that the dissociation of basal and stimulated nitric oxide release may play a pathophysiological role at an early stage of heart failure.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundRemodeling of infarcted and noninfarcted ventricular regions, infarct expansion, shape distortion, and global left ventricular (LV) dilation influence LV performance and survival. The effect of chronic exercise, initiated early or late after infarction, on remodeling, hemodynamics, and survival has not been studied.Methods and ResultsA total of 156 rats were randomized after coronary artery occlusion or sham operation to remain sedentary or to start with swim training 4 days or 21 days after coronary occlusion, which was continued over 8 weeks (6 days per week, 90 minutes per day). These intervals after coronary artery ligation were chosen because final size of infarction is well reached after 4 days; histological evolution of scar healing is still in progress, and after 21 days, histological scar healing is completed. At 8 weeks, hemodynamics were measured and LV dilation quantitated by passive pressure-volume curves. In groups with small (≤35%) and large (>35%) infarcts, the area enclosed by endocardial circumference, infarct size, LV diameter, scar thickness, and septal thickness were measured in stained transverse serial LV sections to assess aneurysmal shape distortion and the response of infarcted and noninfarcted myocardia. Survival was not influenced by infarction or exercise alone. In rats with small infarcts, LV volume and shape and long-term survival were not altered by chronic exercise initiated early or late after coronary artery ligation. Mortality rose in animals with large infarction as a result of exercise (P< .0001) and was 47.6% with early exercise and 26.7% with late exercise (P< .05, early versus late). Infarct size in rats with early exercise (48±3%) was similar compared with infarct size of rats with late exercise (46±2%,P= NS compared with early exercise). Exercise did not affect LV dysfunction (assessed by systolic and end-diastolic pressures and dP/dtmax) in survivors of small and large infarctions. LV volumes increased (P< .05) in sedentary rats by large infarction (n=13, 0.48±0.04 mL) compared with volumes after sham operation (n=33, 0.33±0.03 mL) and with exercise (early, n=11, 0.56±0.04 mL; late, n=11, 0.65±0.04;P< .05 versus sedentary). In nonsurvivors from early exercise, the area enclosed by LV endocardial circumference (which corresponds to LV volume) was increased by 195%, LV diameter was increased by 60%, and scar thickness was reduced by 37% (P< .05 versus respective control). Septal thickness increased in survivors by exercise (+25%) but decreased (−28.6%) in nonsurvivors (P< .0001 versus respective control).ConclusionsEndurance training in rats after small infarction, whether started early or late after left coronary artery ligation, was well tolerated without changes in LV volume, shape, hemodynamics, and long-term survival. Endurance training in rats with large infarction decreased overall survivalP< .0001). In survivors from late exercise, training caused aggravation of global LV dilation without additional shape changes. Endurance training after large infarction caused aggravation of remodeling to a degree that was not compatible with life in 27% of the rats with late exercise and in 48% with early exercise after coronary artery ligation, despite similar exercise. This was explained by extensive remodeling that was most pronounced in nonsurvivors from early exercise. In these rats, severe global LV dilation, distortion of LV shape, scar thinning, and a paradoxic reduction of septal thickness, ie, mismatch of infarcted and noninfarcted myocardia, were observed.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundSynchronized cardioversion is generally accepted as safe for the treatment of ventricular tachycardia and atrial fibrillation when shocks are synchronized to the R wave and delivered transthoracically. However, others have shown that during attempted transvenous cardioversion of rapid ventricular tachycardia, ventricular fibrillation (VF) may be induced. It was our objective to evaluate conditions (short and irregular cycle lengths [CL]) under which VF might be induced during synchronized electrical conversion of atrial fibrillation with transvenous electrodes.Methods and ResultsIn 16 sheep (weight, 62±7.8 kg), atrial defibrillation thresholds (ADFT) were determined for a 3-ms/3-ms biphasic shock delivered between two catheters each having 6-cm coil electrodes, one in the great cardiac vein under the left atrial appendage and one in the right atrial appendage along the anterolateral atrioventricular groove. A hexapolar mapping catheter was positioned in the right ventricular apex for shock synchronization. In 8 sheep (group A), a shock intensity 20 V less than the ADFT was used for testing, and in the remaining 8 sheep (group B), a shock intensity of twice ADFT was used. With a modified extrastimulus technique, a basic train of eight stimuli alone (part 1) and with single (part 2) and double (part 3) extrastimuli were applied to right ventricular plunge electrodes. Atrial defibrillation shocks were delivered synchronized to the last depolarization. In part 4, shocks were delivered during atrial fibrillation. The precedting CL was evaluated over a range of 150 to 1000 milliseconds. Shocks were also delayed 2, 20, 50, and 100 milliseconds after the last depolarization from the stimulus (parts 1 through 3) or intrinsic depolarization (part 4). The mean ADFT for group A was 127±48 V, 0.71±0.60 J and for group B, 136±37 V, 0.79±0.42 J (NS,P> .15). Of 1870 shocks delivered, 11 episodes of VF were induced. Group A had no episodes of VF in part 1, two episodes of VF in part 2 (CL, 240 and 230 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 280 milliseconds with 2-millisecond delay) and 4 (CL, 240 milliseconds with 100-millisecond delay). Group B had two episodes in part 1 (CL, 250 and 300 milliseconds with 20-millisecond delay), three episodes in part 2 (CL, 230, 230, and 250 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 260 milliseconds with 2-millisecond delay) and 4 (198 milliseconds with 100-millisecond delay). No episodes of VF were induced for shocks delivered after a CL >300 milliseconds.ConclusionsSynchronized transvenous atrial defibrillation shocks delivered on beats with a short preceding ventricular cycle length (<300 milliseconds) are associated with a significantly increased risk of initiation of VF. To decrease the risk of ventricular proarrhythmia, short CLs should be avoided.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundAntiarrhythmic therapy of ventricular tachycardia is associated with decreased efficacy and increased proarrhythmia in patients with congestive heart failure, but the explanation for these observations is not known. This study examined the interaction of ventricular dilatation andd-sotalol in a model of reentry ventricular tachycardia.Methods and ResultsThin epicardial layers of anisotropic myocardium were created in Langendorff-perfused rabbit left ventricles by a cryoprocedure. A fluid-filled, latex balloon was secured within the left ventricle to change ventricular volume. Sustained reentrant ventricular tachycardia, around a central cryolesion, was induced by rapid pacing in all preparations (n=7). Epicardial mapping was performed through 248 electrodes. Single premature beats introduced within the reentry circuit were used to define the excitable gap. Dilatation did not influence ventricular tachycardia cycle length or conduction velocity. A 1.25-mL increase in left ventricular volume widened the excitable gap by 12% (range, 5% to 29%) (P< .001) because of a decrease in myocardial refractoriness. d-Sotalol (final concentration, 10 mg/L) narrowed the excitable gap 18%(range, 7% to 29%) (P= .002) in the undilated left ventricle. d-Sotalol was less effective in the dilated left ventricle, narrowing the excitable gap only 9%, a difference that was not statistically significant. During pacing to induce or terminate tachycardia, tachycardia acceleration was observed significantly more frequently in the dilated than in the undilated ventricle. Ventricular tachycardia acceleration was due to the development of double-wave reentry (two successive waves traveling in the same circuit in the same direction). d-Sotalol, which narrowed the excitable gap, prevented tachycardia acceleration and double-wave reentry.ConclusionsAntiarrhythmic efficacy may be decreased by dilatation because of a widening of the initial excitable gap and a decrease in the gap-narrowing effect of these agents. Double- wave reentry, more likely with a widening of excitable gap, may partially explain tachycardia acceleration in the dilated ventricle.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The history of the antithrombotic agents- aspirin, heparin, warfarin, and the thrombolytics -is a rich and lively odyssey of serendipity, perseverance, vision, and conflict involving a number of striking personalities. The history of aspirin spans ages and continents from Hippocrates' analgesic for women in labor to the rediscovery of the white willow bark by English country scholar Reverend Edward Stone. Bayer chemist Felix Hoffmann reinvented aspirin for his ailing father; suburban physician L.L. Craven pioneered the prophylactic antithrombotic uses of aspirin; and Sir John Vane elucidated aspirin's mechanism of action as the inhibition of prostaglandin synthetase. Heparin was discovered by McLean, working as a medical student in 1915 in search of a pure procoagulant in dog liver. His original impure material differed somewhat from today's heparin, but purified heparin was rapidly accepted for a myriad of clinical uses; to this day, diverse new properties of this complex glycosaminoglycan continue to be elucidated. The oral anticoagulants emerged from veterinary research in the 1920s on a hemorrhagic disorder afflicting cattle that consumed spoiled sweet clover hay. Several chance encounters led Karl Link and his University of Wisconsin team to the identification of dicumarol as the offending agent in 1939 and its widespread therapeutic use by Wright and others in the 1940s. Link later developed warfarin as a rodenticide, but its use in humans soon followed in the 1950s. Vitamin K was discovered in the 1930s; its involvement in the mechanism of the anticoagulant agents was not delineated until the 1970s. The intrinsic ability of clotted blood to liquify and the fibrinolytic properties of normal urine were noted in the 1800s. Tillett and Sherry's group stumbled on the fibrinolytic properties of streptokinase in the 1930s and pioneered the therapeutic use of streptokinase in the 1940s and of urokinase in the 1960s. Several teams found tissue-type plasminogen activator in various body sites beginning in the 1940s, leading to its cloning and widespread use in the 1980s; anisoylated plasminogen- streptokinase activator complex is an example of rational drug design. The discoverers of these diverse agents have not only provided physicians with a potent armamentarium of antithrombotic drugs but also helped elucidate much basic science and vividly demonstrated the merits of perseverance, independent thought, and adherance to the scientific method.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundEach month, the number of transplant candidates added to the waiting list exceeds the number of transplantations performed, and many outpatients deteriorate to require transplantation urgently. The current list of 2400 candidates and the average wait of 8 months continue to increase.Methods and ResultsTo determine the size at which the outpatient and critical candidate pools will stabilize, population models were constructed using current statistics for donor hearts, candidate listing, sudden death, and outpatient decline to urgent status and revised to predict the impact of alterations in policies of candidate listing. If current practices continue, within 48 months the predicted list will stabilize as the sum of an estimated 270 hospitalized candidates, among whom, together with newly listed urgent candidates, all hearts will be distributed and 3700 outpatient candidates with virtually no chance of transplantation unless they deteriorate to an urgent status. Decreasing the upper age limit now to 55 years would reduce the number listed each month by 30% and result within 48 months in a list of only 1490. The list could also be decreased by 30%, however, if it were possible to list only a candidate group with an 80% chance (compared with 52% estimated currently) of sudden death or deterioration during the next year. With this strategy, the waiting list would equilibrate within 48 months to one-third the current size, with 50% of hearts for outpatient candidates, who would then have an 11% chance each month of receiving a heart compared with 0% if recent policies prevail. Total deaths, with and without transplantation, would be minimized by this rigorous selection of outpatient candidates.ConclusionsThis study implies that immediate provisions should be made to limit candidate listing and revise expectations to reflect the diminishing likelihood of transplantation for outpatient candidates. Future emphasis should be on improved selection of candidates at highest risk without transplantation.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A comprehensive review of physiological and molecular biological evidence refutes claims for synthesis of renin by cardiac and vascular tissues. Cardiovascular tissue renin completely disappears after binephrectomy. Residual putative reninlike activity, where investigated, has had the characteristics of lysosomal acid proteases. Occasional reports of renin or renin mRNA in vascular and cardiac tissues can be ascribed to failure to remove the kidneys 24 hours beforehand, overloading of detection systems, problems with stringency in identification, and illegitimate transcripts after more than 25 cycles of polymerase chain reaction. Others, using more stringent criteria, have failed to detect cardiac and vascular renin mRNA. Accordingly, a growing number of investigators have concluded that the kidneys are the only source of cardiovascular tissue renin. Although prorenin is secreted from extrarenal tissues as well as from the kidneys, there is no evidence that it is ever converted to renin in the circulation. The kidney is the only tissue with known capacity to convert prorenin to renin and to secrete active renin into the circulation. Accordingly, renin of renal origin determines plasma and hence, extracellular fluid renin levels. In these loci, angiotensin (Ang) I, formed by renin cleavage of circulating and interstitial fluid angiotensinogen, is in turn cleaved by angiotensin converting enzyme, located in plasma and extracellular fluids and on the luminal surface of pulmonary and systemic vascular endothelial cells, to Ang II, which perfuses and bathes the heart and vasculature. Consistent with this model, plasma renin and angiotensin and the antihypertensive action of renin inhibitors, converting enzyme inhibitor, or Ang II antagonists all disappear after binephrectomy. Thus, the plasma renin level, via Ang II formation, determines renin system vasoconstrictor activity, the antihypertensive potential of anti-renin system drugs, and the risk of heart attack in hypertensive patients. This analysis redirects renin research to renal mechanisms that create the plasma renin level, to renal prorenin biosynthesis and its processing to renin, and to their regulated secretion, extracellular distribution, and possible binding to by target tissues. In this context, it is still possible that changes in circulating and interstitial renin substrate or available converting enzyme might exert subtle modulating influences on Ang II formation. However, this analysis redefines the importance of plasma renin measurements to assess clinical situations, because plasma renin is the only known initiator driving the cardiovascular renin-angiotensin system, and its strength can be measured.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundTo be used optimally, new interventional devices (stent, lasers, atherectomy catheters) must be carefully evaluated in terms of optimal patient and lesion selection, technique of use, expected acute success and complications, and long-term results. Sources for that information include singlecenter and multicenter (single-device) reports, although randomized trials may then be performed to provide a more definitive picture of any clinical benefits. One interim option, however, consists of carefully collected registry data. The purpose of this article is to review data collected in the National Heart, Lung, and Blood Institute-funded New Approaches to Coronary Intervention (NACI) Registry and to compare them with existing reports.Methods and ResultsNACI is an independent, investigatordriven effort that seeks to collect uniform data on patients undergoing treatment with one of several investigational devices and thereby provide an unbiased report of procedure outcome. Between November 1990 and November 1992, 36 participating centers treated a total of 3201 lesions in 2835 patients, using one of seven study devices: directional atherectomy (1084 lesions), transluminal extraction atherectomy (240 lesions), rotational atherectomy (349 lesions), Palmaz-Schatz stent (674 lesions), Gianturco-Roubin stent (213 lesions), and the Advanced Interventional Systems (474 lesions) or Spectranetics (167 lesions) excimer lasers. Data on each procedure were recorded on a unique modular database that captured the reason for (and interim result after) each device use. Device success (defined here as stenosis improvement by ≥20% and a residual stenosis <50% after new device use) was 66.5% overall. Adjunctive angioplasty was used in 75.5% of lesions, either before (25.9%) or after (43.5%) new device use, yielding an overall lesion success (≥20% stenosis improvement with a final residual stenosis <50% after all devices) of 92.2%. Adjunctive angioplasty after new device use produced further enlargement in minimal lumen diameter (from 2.2 to 2.7 mm) and further reduction in residual stenosis (26.4% to 16.1%) compared with the results present after use of the new devices themselves. Major complications consisting of death (1.6%), Q-wave myocardial infarction (1.3%), or emergency bypass surgery (1.7%) occurred in 4.0% of patients range, 2.6% to 8.7% across devices). Procedural success, defined as lesion success in all new device-treated lesions without a major complication, was achieved in 90.8% of patients, with a median length of hospital stay of 4 days.ConclusionsNACI illustrates the type of information that can be obtained in a registry format that examines the acute angiographic and clinical results of new devices according to uniform definitions. Although no registry can substitute for formal interdevice trials, registries such as this can supplement earlier single-center and multicenter reports. In doing so, they can help focus subsequent randomized interdevice comparisons on lesion types for which two or more devices have promising acute results. Given the substantial interdevice differences in baseline patient and lesion characteristics found in NACI, simple “head-to-head” comparison of the results of different devices might give misleading impressions and should be avoided unless such comparisons are restricted to carefully matched patient and lesion subgroups.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID