摘要:

ABSTRACTThe effect of medical and surgical treatment on subsequent sudden cardiac death was assessed in 13,476 patients in the Coronary Artery Surgery Study registry who had significant coronary artery disease, operable vessels, and no significant valvular disease. (Patients were assigned to medical or surgical therapy on the basis of clinical judgment and not according to a randomization scheme; therefore, biases associated with unknown variables could not be evaluated.) Sudden cardiac death occurred in 452 patients (3.4%) during a mean follow-up of 4.6 years. Five year survival free of sudden death for medically treated patients was 94 ± 0.3%, and that for surgically treated patients was 98 + 0.2% (p < .0001). Twelve baseline clinical, electrocardiographic, and angiographic variables were significantly different between patients alive at the last follow-up and those suffering sudden death. Data on these variables were available for 11,508 patients. Sudden death occurred in 257 (4.9%) of 5258 medically treated and 101 (1 6%) of 6250 surgically treated patients. In a high-risk patient subset with three-vessel disease and history of congestive heart failure, 91% of surgically treated patients had not suffered sudden death compared with 69% of medically treated patients. After Cox survival analysis was used to correct for baseline variables, surgical treatment had an independent effect on sudden death (p < .0001). This reduction was most pronounced in high-risk patients.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTNitroglycerin acts, in part, to reduce arterial impedance, and thus left ventricular work. The reduction in arterial impedance is largely attributable to a fall in systemic vascular resistance, but may also be due to an increased distensibility of the arterial tree. In this study, volume distensibility of forearm arteries was calculated from measurements of pulse-wave velocity before and during intravenous nitroglycerin infusion. Since a fall in blood pressure itself increases arterial distensibility, the induced blood pressure change was controlled as a variable by repeating the measurements with the subject's forearm in a plastic cylinder and repeating the measurements at a variety of altered cylinder pressures. At every studied pressure, nitroglycerin infusion increased forearm arterial distensibility, demonstrating another way in which nitroglycerin reduces left ventricular afterload. Since the pulsatile portion of cardiac work is approximately 10% of total work, the magnitude of this nitroglycerin effect on cardiac function is probably small.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTThe long-term effects of antianginal therapy on coronary blood flow and myocardial metabolism were studied in 35 patients with chronic stable angina. Arterial and coronary sinus blood samples and coronary blood flow measurements were obtained before and after 1 month of oral administration of propranolol or of the calcium antagonist nicardipine. When the data obtained at a fixed heart rate (10% to 15% above the pretreatment sinus rhythm) were compared, no significant differences were evidenced between the propranolol and the nicardipine groups. Coronary blood flow and myocardial oxygen uptake were unchanged with both drugs. Myocardial lactate uptake increased in 1 1 patients of the propranolol group (from - 2 + 42 to 66 + 47 g.mol/min, p < .001) and in 1 1 patients of the nicardipine group (from 0 + 36 to 31 ± 29 gnmol/min, p < .001). In these 22 patients, the increase in lactate uptake was accompanied by reductions in uptake of free fatty acids and by a decrease in the coronary sinus concentration of thromboxane B, from 131 ± 87 to 61 + 32 pg/ml (p < .01), whereas the transcardiac release of prostacyclin increased. None of these changes in free fatty acids or in prostanoid handling were observed in the nine patients (five in the propranolol and four in the nicardipine group) in whom lactate uptake was not augmented. During pacing-induced tachycardia, the metabolic effects of the two drugs appeared different. Myocardial lactate uptake decreased more in the patients receiving propranolol than in those receiving nicardipine and the combined productions of alanine and glutamine rose by 3.2 + 5.8 gmol/min in the propranolol group while it decreased by 3.1 + 8.2,umol/min in the nicardipine group (p < .025 propranolol vs nicardipine). In conclusion, longterm antianginal therapy with propranolol or nicardipine improved several markers of myocardial ischemia in approximately two-thirds of the patients. Although the changes observed at low heart rates were similar with the two drugs, the data also suggest that better metabolic protection is provided by the calcium antagonist during pacing-induced tachycardia.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTThe effects of abrupt withdrawal or continuation of fl-blockade therapy during acute myocardial infarction were evaluated in 326 patients participating in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). Thirty-nine patients previously receiving a f8-blocker and randomly selected for withdrawal of fl-blockers and placebo treatment during infarction (group 1) were compared with 272 patients previously untreated with fl-blockers who were also randomly assigned to placebo therapy (group 2). There were no significant differences between the two groups in MB creatine kinase isoenzyme (15.8 10.9 vs 18.2 + 14.4 g-eq/m2, respectively) estimates of infarct size, radionuclide-determined left ventricular ejection fractions within 18 hr of infarction (0.44 0.15 vs 0.47 0.16) or 10 days later (0.42 0.14 vs 0.47 0.16), creatine kinase-determined incidence of infarct extension (13% vs 6%), congestive heart failure (43% vs 37%), nonfatal ventricular fibrillation (5% vs 7%), or in-hospital mortality (13% vs 9%). Patients in group 1 had more recurrent ischemic chest pain (p = .002) within the first 24 hr after infarction, but not thereafter. However, this did not appear to be related to a rebound increase in systolic blood pressure, heart rate, or double product. In a separate analysis, 20 propranolol-eligible group 1 patients randomly selected for withdrawal of fl-blockade (group 3) were compared with 15 patients randomly selected for continuation of prior fiblockade therapy (group 4). This comparison yielded similar results. These data indicate that the,f-blockade withdrawal phenomenon is not a major clinical problem in patients with acute myocardial infarction. f-Blockade therapy can be discontinued abruptly during acute myocardial infarction if clinically indicated.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTProspective characterization of pharmacodynamics of tissue-type plasminogen activator (t-PA) is needed for diverse clinical applications. Accordingly, we used physiologically based, computer simulation of participating biochemical reactions in response to concentrations of circulating t-PA seen with infusions of 1 to 7 hr duration in 45 patients. Predicted values were compared with those from a "training set" obtained in six patients given t-PA for coronary thrombosis and six receiving therapy for peripheral arterial occlusion. Subsequently, results of simulation were compared prospectively with observations from a "test set" of 33 consecutive patients given low doses of t-PA for as long as 7 hr or higher doses for 1 to 2 hr and with data from 101 patients given t-PA in the European Cooperative Trial. Fits between observed and predicted values were close. Based on observations in the training set, the at2-macroglobulin reaction with circulating plasmin and ongoing synthesis of plasminogen were incorporated in the simulations. Fibrinogenolysis in vitro was documented despite supplementation of samples with aprotinin, particularly when concentrations of t-PA were high. This phenomenon can lead to overestimation of fibrinogen depletion and was found to be obviated by the use of PPACK, a novel serine protease inhibitor. Results indicate that the simulation approach developed permits economic, prospective evaluation of regimens of t-PA suitable for diverse conditions and delineation of the impact of individual constituents and reactions on pharmacodynamics of t-PA and on the risk of induction of a systemic lytic state.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTAlthough thromboxane A2 is a potent platelet agonist and vasoconstrictor in vitro, our knowledge of its pathophysiologic importance in human disease is limited. To facilitate the elucidation of its role in vivo, we sought to define a human syndrome in which pharmacologic interventions designed to inhibit the biosynthesis or biologic actions of thromboxane A2 might be appropriately assessed. Patients with severe peripheral vascular disease were selected on the basis of elevated plasma,8-thromboglobulin and circulating platelet aggregates and compared with healthy, age-matched control subjects. In addition to the platelet indexes, their bleeding time was shorter and excretion of 2,3-dinor-thromboxane B2, a noninvasive index of thromboxane formation in vivo, and 2,3-dinor-6-ketoprostaglandin F,a, the major urinary metabolite of prostacyclin, was markely increased. A selective inhibitor of thromboxane synthase, imidazo (1,5-2) pyridine-5-hexanoic acid, was administered to these patients under randomized, double-blind, controlled conditions. Platelet aggregation ex vivo, the circulating platelet aggregate ratio, and the bleeding time were all unaltered, despite almost maximal inhibition of platelet thromboxane formation 1 hr after dosing. By contrast, pronounced inhibition of aggregation was observed when platelet cyclooxygenase was inhibited by aspirin. During long-term dosing with the synthase inhibitor, inhibition of thromboxane biosynthesis was incomplete, which would permit continued thromboxane-dependent platelet aggregation to occur. However, the failure of enzyme blockade to influence platelet function at the time of maximal drug action, despite efficient inhibition of serum thromboxane B2, suggests that accumulation of proaggregatory endoperoxides is also likely to have contributed to the persistence of platelet activation. We have characterized a human preparation in which platelet activation coexists with increased thromboxane biosynthesis. In this setting, platelet activation persists despite long-term administration of a thromboxane synthase inhibitor in a dosing regimen representative of that employed in clinical trials. Prolongation of drug action and combination with antagonists of the shared endoperoxide/thromboxane A2 receptor may be necessary to assess the potential of selective inhibition of thromboxane synthase as a therapeutic strategy in man.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTAs the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressurevolume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 3.35 (+SD) to 6.38 0.96 mm Hg/ml (p < .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tenses may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTWe compared two methods of delivering single damped sine-wave defibrillator pulses to the coronary sinus orifice in 20 dogs. Ten dogs had "unipolar" (coronary sinus to precordial disc) and 10 had "bipolar" (coronary sinus proximal to coronary sinus distal electrode) discharges. Delivered voltage, current, and energy were recorded during each pulse. Electrophysiologic testing was done before and 4 weeks after the procedure. Histologic examination of the atrioventricular groove was done at 1 mm serial sections. For the unipolar configuration a 200 J defibrillator pulse resulted in a peak voltage of 3370 125 V, a peak current of 21 + 4 A, and a delivered energy of 253 ± 29 J as compared with 3010 ± 99 V, 70 ± 4 A, and 144 18 J, respectively, for the bipolar configuration (p < .001). Three dogs (two with bipolar, one with unipolar pulses) had gross coronary sinus rupture and died from acute pericardial tamponade. In addition, irrespective of electrode configuration, all dogs showed microscopic rupture of the coronary sinus internal elastic membrane. Transmural atrial scarring occurred in all 10 dogs that received a unipolar pulse but in only two dogs that received a bipolar pulse (p = .0004). Unlike the atrium, injury to the left ventricle was limited in both groups. Similarly, injury to the periannular myocardium was inconsistent and not transmural in either group. No significant electrophysiologic changes were observed. With the present technique, unipolar rather than bipolar catheter-mediated defibrillator pulses result in transmural atrial injury that might prevent accessory pathway conduction. Regardless of electrode configuration, high-energy defibrillator pulses consistently cause some degree of coronary sinus rupture, most likely related to a barotraumatic mechanism.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTEncainide, a class IC antiarrhythmic agent, has been associated with proarrhythmic responses of ventricular tachycardia and fibrillation requiring defibrillation in patients. We examined the short-term effects of intravenous encainide and its two major metabolites, O-demethyl-encainide (ODE) and 3-methoxy-ODE (MODE), on the energy requirements for successful defibrillation in 25 pentobarbital-anesthetized, open-chest dogs. Truncated exponential (60% tilt) defibrillation shocks were administered through right atrial spring and left ventricular epicardial patch electrodes identical to those used in man with the automatic implantable defibrillator. At baseline multiple shocks of varying energy were applied to construct curves of percent successful defibrillation as a function of energy (DF curves) for each animal. Encainide, ODE, or MODE was then infused in loading and maintenance doses to achieve QRS widening of 20% to 50%. Saline was administered to animals serving as controls. Determination of the DF curve was repeated, after which the infusion was discontinued. After 1 hr washout period, an additional DF curve was constructed. The data were analyzed by logistic regression,and the energies required for 50% successful defibrillation (E50) were compared. No significant differences existed between the four groups in body or heart weight, extent of QRS widening, or baseline E50 values. After administration of encainide and ODE, the E50 increased by 129 ± 43%(p < .001) and 76 + 34% (p < .005), respectively. Return of E50 toward baseline was observed after the washout periods in both groups (p < .025), demonstrating the reversibility of the drugs' effects. No significant increase in E50 was observed after administration of MODE, and the results were not statistically different from those in the control group. We conclude that both encainide and ODE greatly increase the energy required for successful defibrillation, while MODE does not exert a significant effect. Also, their effect on defibrillation cannot be predicted by plasma drug concentration, extent of QRS widening, or increase in ventricular refractoriness.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

ABSTRACTThe effects of therapeutic levels of quinidine were studied in an ischemic gap preparation of reflected reentry. The preparation consisted of a Purkinje fiber mounted in a three-compartment chamber. A narrow central compartment was perfused with a solution prepared to mimic the extracellular milieu at a site of ischemia. Quinidine in concentrations that exert little effect on normal Purkinje tissue, 1 to 2,ug/ml, greatly impaired conduction and markedly prolonged refractoriness across the ischemic gap. The drug effected these changes by (1) extending the inexcitable zone within the depressed region, (2) decreasing the amplitude of the input signal entering this zone, and (3) decreasing the excitability of the tissue beyond the depressed zone (evaluated by current clamp techniques). These actions of the drug produced both antiarrhythmic and proarrhythmic effects. When the initial level of conduction impairment was high, quinidine totally suppressed reflected reentry at all frequencies by precipitating complete anterograde conduction block. At intermediate levels of block, the drug generally caused a prominent shift of the frequency dependence of reentrant activity to lower stimulation rates. Finally, when conduction was relatively less impaired, quinidine created the conditions for reflected reentry to occur. Our results suggest that the heart rate dependence of reentrant arrhythmias might be of prognostic value in the administration of antiarrhythmic drugs.

ISSN:0009-7322    

出版商:OVID    

年代:1986

数据来源: OVID