美托洛尔辅以小剂量甲状腺激素治疗扩张型心肌病心力衰竭

目的:探讨β—受体阻滞剂治疗扩张型心肌病(DCM)心力衰竭早期加用小剂量甲状腺激素对药物耐受性的影响及其临床意义。方法:27例DCM患者,随机分为M(美托洛尔)和MT(美托洛尔加甲状腺片)组,甲状腺片(10mg,日一次)在开始应用美托洛尔时口服,共2周。心功能、运动试验、T3、T4、rT_3和TSH于用药前和用药6周时各检查1次。结果:M组有4例出现低血压,其中1例有心衰加重表现;MT组仅1例有一过性低血压,且心功能改善较M组早。结论:加用小剂量甲状腺激素有利于提高DCM患者对β—受体阻滞剂治疗的耐受性。     

EFFECT OF TEMOCAPRIL ON HAEMODYNAMIC AND HUMORAL RESPONSES TO EXERCISE IN PATIENTS WITH MILD ESSENTIAL HYPERTENSION

1. This study was carried out to evaluate the effect of temocapril on haemodynamic and humoral responses to exercise in nine patients with mild essential hypertension (WHO stages I and II). 2. After a 4-week placebo period, temocapril was administered at a dose of 1.0 mg once daily for 2–4 weeks. Graded submaximal bicycle ergometer exercise was performed before and after temocapril treatment, and the changes in arterial blood pressure, heart rate, cardiac output (CO), and systemic vascular resistance (SVR) were evaluated. In addition, the plasma norepinephrine (NE) level was determined both at rest and peak exercise before and after temocapril treatment. 3. Both the systolic and diastolic blood pressure were reduced at rest and during exercise by temocapril treatment. No significant change in the resting heart rate and CO was observed, and the exercise-induced increase of these parameters was also not affected by temocapril. In contrast, the resting SVR was significantly decreased by temocapril, although the exercise SVR was similar during both temocapril and placebo treatment. 4. Although there was no significant change in the plasma NE level with temocapril treatment, the exercise-induced increase of plasma NE was significantly suppressed by temocapril. 5. These results indicate that temocapril reduces the blood pressure without causing any significant changes in the heart rate and CO at rest, and that it does not produce any changes in the haemodynamic response to exercise.     

Evaluation of a sustained-release buccal nitroglycerin preparation in stable angina pectoris

The efficacy of a 2.5 mg sustained-release buccal nitroglycerin preparation given 8-hourly in effort-induced stable angina pectoris was investigated by means of graded exercise testing in 15 patients. An initial double-blind crossover study, compared with a placebo (duration six days) was followed by a further 15-day open treatment period on the active drug. Exercise testing was carried out 2 and 7 h after tablet administration at the conclusion of active treatment in the double-blind phase, and 2 h after tablet administration at the conclusion of the open treatment phase. Workload and exercise duration were significantly increased and mean electrocardiographic ST segment depression and ST segment recovery time significantly reduced by buccal nitroglycerin in the initial phase of the study, and these improvements were maintained over the subsequent 15-day assessment period. Systolic blood pressure at rest was significantly decreased by active treatment; other haemodynamic parameters remained unchanged. The study demonstrated the efficacy of sustained-release buccal nitroglycerin in effort-induced stable angina pectoris, and an absence of (+) tolerance to the therapeutic effects of this mode of nitrate administration.     

Effects of long-term treatment with verapamil on left ventricular function and myocardial blood flow in patients with dilated cardiomyopathy without overt heart failure

Myocardial blood flow (MBF) abnormalities are present in early stage dilated cardiomyopathy (DCM) and have been attributed to coronary microvascular abnormalities. The favorable effects of verapamil on coronary microcirculation might indicate its use in early stage DCM. We assessed the safety of long-term combination therapy of verapamil and enalapril and its effects on both left ventricular function and myocardial perfusion compared with enalapril alone in 18 patients with DCM (15 men, 3 women; mean age, 50+/-9 years) without overt heart failure (NYHA class I-II). At baseline and after 6 months of randomized treatment with either enalapril (10-20 mg) (nine patients, group 1) or enalapril (10-20 mg) and verapamil (120-240 mg) (nine patients, group 2), left ventricular function was assessed at rest, during handgrip, and during bicycle exercise by equilibrium radionuclide angiography. Mean MBF was measured at rest and after dipyridamole by positron emission tomography (PET) and 13N-ammonia as a flow tracer. At baseline, the two groups had reduced left ventricular ejection fraction at rest, which was further impaired during isometric exercise, but increased at peak bicycle exercise. MBF was similarly reduced in the two groups at rest and during dipyridamole. During treatment, no adverse events occurred in either group. After 6 months there was no significant difference in the main study variables either between the two groups or within each group before and after treatment. Long-term combination therapy with verapamil and enalapril is safe in patients with DCM without overt heart failure. Despite no favorable effect on myocardial perfusion, combined treatment prevented deterioration of left ventricular function, similarly to enalapril alone.     

A randomized cross-over study of enalapril in congestive heart failure: Haemodynamic and hormonal effects during rest and exercise

Summary We performed a randomized double-blind placebo controlled cross-over study of enalapril in 16 patients with chronic congestive heart failure, to assess haemodynamic and hormonal effects at rest and on exercise. Acute effects were measured 4 h after enalapril 10 mg, and chronic effects after 6 weeks treatment with enalapril 10–20 mg per day.Exercise tolerance, assessed by the duration of a maximal bicycle ergometer test, was not altered by enalapril. Mean blood pressure was reduced after enalapril, at rest and on exercise, acutely by 7% and 8% respectively, and chronically by 14% and 16%. Systemic vascular resistance was reduced by 16% at rest both acutely (NS) and chronically (p<0.05). The resting pulmonary capillary wedge pressure was reduced by 28% with chronic treatment. In the acute study, total body oxygen consumption on exercise was 26% higher after enalapril. Chronically, resting oxygen consumption was reduced by 13% after enalapril, with mixed venous oxygen saturation increasing by 16%.In the acute study enalapril increased plasma renin activity at rest and on exercise by 181% and by 189%, and reduced aldosterone by 49% (NS) and 39% (p<0.05), and these effects were sustained after 6 weeks. Enalapril increased antidiuretic hormone concentrations at rest acutely by 73% (NS) and chronically by 34% (p<0.05) but not on exercise; the increase in the acute study correlated with plasma enalaprilat levels (r=0.66, p<0.05). Enalapril did not alter plasma catecholamine concentrations.Patients preferred enalapril to placebo, and radiographic heart size was reduced during chronic treatment. There were no serious adverse effects.We conclude that enalapril is an effective angiotensin converting enzyme inhibitor of clinical value in chronic heart failure, but study design and methods of assessment of benefit can have a major influence on the results of pharmacological studies in such patients.     

Acute effects of nisoldipine, propranolol, and their combination in patients with chronic stable angina: a double-blind, randomized, cross-over, placebo-controlled study.

We studied the short-term effects of oral administration of nisoldipine (10 mg) and propranolol (80 mg) alone and in combination in 14 patients with chronic exertional angina pectoris in a double-blind, randomized, cross-over study. The 14 patients (13 men and 1 woman, mean age 56 +/- 7 years) performed symptoms-limited bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration, and time to 1-mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by drugs alone and in combination. Propranolol and nisoldipine alone improved exercise duration similarly and as well as the combination; however, a different response to the three pharmacologic interventions was found in patients treated with single drugs. The improvement in exercise tolerance was associated with rate-pressure product values at peak exercise, unchanged after nisoldipine and significantly reduced after both propranolol alone and in combination. After placebo, all patients had exercise-induced angina, in 9, 8, and 4 patients after nisoldipine, propranolol, and the combination of the two drugs, respectively. Nisoldipine is effective in the treatment of effort angina and its combination with propranolol may be useful and superior in patients who show poor response to monotherapy.     

有氧运动对慢性心力衰竭患者骨骼肌功能的影响

目的探讨有氧运动训练对慢性心力衰竭（CHF）患者骨骼肌功能的影响。方法选取心功能稳定的CHF患者38例,随机分为2组：治疗组（n=20）及对照组（n=18）,2组患者均给予内科常规治疗,治疗组在此基础上同时进行运动训练;并分别在治疗前及治疗16周后对2组患者进行运动耐力、血乳酸、丙二醛、琥珀酸脱氢酶和骨骼肌纤维类型比较。结果治疗组显著增加运动耐力,降低血乳酸和丙二醛水平,差异有统计学意义（P均〈0．05）。琥珀酸脱氢酶含量显著增高（P〈0．05）,Ⅰ型肌纤维含量增加,Ⅱ型肌纤维含量下降。结论有氧运动训练可以改善骨骼肌功能,增加患者运动耐力。     

Effects of trimetazidine on left ventricular function in patients with type 2 diabetes and heart failure

Congestive heart failure and type 2 diabetes have a deleterious prognosis when combined. Trimetazidine, a metabolic agent with anti-ischemic properties, reduces fatty acid beta-oxidation via decreased 3-ketoacyl-coenzyme-A thiolase activity thereby facilitating energy production via the glycolytic pathway. OBJECTIVES: To assess myocardial function by Tissue Doppler Imaging (TDI) after one month of trimetazidine (Vastarel) added-on conventional treatment in patients with type 2 diabetes and heart failure. METHODS: Twenty diabetic patients with ischemic heart failure (mean age 66 years; NYHA class II-III) were randomized to trimetazidine (60 mg daily) or placebo in a double-blind crossover design. Exercise tolerance, 2-dimensional echocardiograms, and TDI (rest and exercise) were studied before and during treatment. RESULTS: Changes in exercise tolerance did not differ in the two groups. Ejection fraction at rest and moderate exercise only improved significantly with trimetazidine when analyzed for the first treatment period. TDI velocities did not change significantly during treatment periods. CONCLUSION: In this early pilot investigation of the effects of trimetazidine in patients with diabetes and heart failure there were only weak signs of improved systolic myocardial function at rest and exercise. The present observations indicate the need of further research to explore the effect of trimetazidine during longer treatment period or with more selected patient population.     

Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study

This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic blood pressure.     

Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients

Previous studies suggested that certain lipid-lowering drugs such as statins suppress ubiquinone, affect mitochondrial function, and may have deleterious effect on skeletal or cardiac muscles with potentially serious clinical consequences, especially in patients with established coronary heart disease and left ventricular dysfunction. In this double-blind study, we assessed the effects of 20 mg simvastatin (S, n = 32) or 200 mg micronized fenofibrate (F, n = 32, control group) on rest and exercise left ventricular function in hypercholesterolemic survivors of a previous Q-wave acute myocardial infarction. Left ventricular radionuclide imaging was performed at rest and during submaximal exercise and global and segmental (nine segment regional wall-motion score) ejection fractions were measured before treatment and 12 weeks later. Serum ubiquinone was reduced after treatment (p = 0.03) in the S but not the F group, whereas total and low-density lipoprotein (LDL) cholesterol were significantly reduced in both groups. Before treatment, mean global ejection fraction was 52.1+/-12.2% and 49.3+/-11.8% at rest in F and S patients, respectively, and increased (56.0+/-13.7% in F and 52.1+/-12.9% in S) at peak exercise (no difference between groups). After treatment, the increase in ejection fraction tended to be lower in S (0) than in F (+3.8%) but not significantly. However, ejection fraction at rest increased after treatment in S (p = 0.009) but not in F. Subgroup analyses indicated that the improvement in rest ejection fraction in S was essentially observed in patients with ejection fraction <40% (n = 8, +6%), whereas it was stable in patients with ejection fraction >40% (+1.8%). Finally, the numbers of akinetic or hypokinetic segments at rest and during exercise were not different in the two groups before and after treatment. Mean maximal exercise load (113+/-23 watts in F vs. 104+/-27 W in S before treatment) was not modified by the treatment (111+/-21 and 104+/-27 W). Thus a 12-week lipid-lowering treatment with either S or F did not negatively alter left ventricular function during exercise in dyslipidemic patients with established coronary heart disease and did not affect their ability to exercise. The improvement in left ventricular function at rest after simvastatin in patients with left ventricular dysfunction warrants confirmation in further studies with large sample size.     

Effect of garlic (Allium sativum) oil on exercise tolerance in patients with coronary artery disease

The effect of six weeks garlic oil administration was observed on cardiac performance and exercise tolerance in 30 patients of coronary artery disease. After initial treadmill stress test, they were administered garlic oil in the dose of four capsules twice a day for 6 weeks and treadmill stress test was repeated. Garlic significantly (P<0.01) reduced heart rate at peak exercise and also significantly reduced the work load upon the heart resulting in better exercise tolerance (P<0.05) as compared to the initial test. It appears to be a good adaptogen to be utilized in patients with coronary artery disease.     

Effects of long-term therapy with oral piroximone on resting hemodynamics, peak aerobic capacity, and the anaerobic threshold in patients with heart failure

Piroximone (MDL 19205), a new imidazole derivative with positive inotropic and vasodilating properties, was administered to 10 patients with congestive heart failure. After acute intravenous (0.90 +/- 0.12 mg/kg, mean +/- SEM) and oral (1.41 +/- 0.18 mg/kg) administration, cardiac index and stroke volume index increased and were accompanied by a decline in systemic vascular resistance, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial pressure was unchanged, but heart rate increased modestly after intravenous piroximone. An increase in premature ventricular contractions was documented in four patients after drug administration. Seven of the 10 patients completed 12 weeks of therapy with piroximone; one patient withdrew after 8 weeks because of deterioration in clinical status; one developed severe ventricular arrhythmias and died after 5 days of treatment; and a drug-induced hepatitis was documented in one subject at 4 weeks. No significant improvement in oxygen uptake at peak exercise and the anaerobic threshold was observed after long-term treatment (assessed at 6 and 12 weeks). Hemodynamic responsiveness to piroximone was sustained in five patients who underwent repeat evaluation at 12 weeks. Thus, long-term treatment with piroximone was not associated with an improvement in maximal and submaximal exercise capacity in patients with congestive heart failure. Serious adverse effects were observed with the administration of this drug.     

Haemodynamic effects of indenolol at rest and after a submaximal workload in essential hypertension

Summary The effect of indenolol on heart rate and blood pressure at rest and after submaximal workload has been studied in 19 patients with established essential hypertension. A stepwise increase from moderate to submaximal exercise was chosen to mimic challenges normally occurring in daily life. After 4 weeks of once a day indenolol therapy a significant, gradual reduction in the following cardiovascular parameters was observed: heart rate at rest fell by 20%, 30% after exercise and 31% after recovery; systolic blood pressure showed a fall of 15% at rest, 19% after workload and 14% after recovery; the reduction in diastolic blood pressure was 15% at rest, 11% after exercise and 12% after recovery. The rate-pressure product was decreased by 32% at rest, 43% after exercise and 42% after recovery. It is concluded that the most important pharmacological effect of indenolol is the significant decrease in myocardial oxygen demand. In patients with essential hypertension indenolol not only produces a definite antihypertensive effect, but it also increases workload tolerance and decreases subjective symptoms during physical activity. Compliance was good and no severe side effects were observed.     

Effect of intravenous and oral pindolol on exercise tolerance and electrocardiographic changes in angina pectoris

The effects of intravenous (0.4 mg) and oral pindolol (5 mg, t.i.d.) on exercise tolerance and electrocardiographic ST-segment changes were investigated in 20 patients with documented coronary artery disease (16 males and 4 females; mean age, 56.7 years). A randomized double-blind crossover design was used, and graded submaximal exercise was performed on a bicycle ergometer. Pindolol significantly decreased heart rate at rest, and during and after exercise. The time intervals before the appearance of ST depression, before anginal pain, and before the cessation of work were significantly increased after beta-adrenergic blockade, and work tolerance was enhanced, both indicating that pindolol is an effective antianginal agent. Angina appeared at a lower heart rate after pindolol. Anginal pain and cessation of work were associated with significantly less ST-segment depression after pindolol, suggesting that the relation between ST depression and myocardial ischemia is altered by beta-adrenergic blockade. The appearance and disappearance of ST-segment changes correlated closely with heart rate during placebo and pindolol treatment. Heart rate thus seems to be a major determinant of ST-segment depression during and after exercise in coronary artery disease.     

Lack of effect of asymmetrical dosage timing of isosorbide-5-mononitrate on nitrate tolerance during long-term administration

Summary Isosorbide 5-mononitrate is an active metabolite of isosorbide dinitrate and possesses many theoretical advantages over its parent drug. However, the development of partial tolerance has been demonstrated when the drug is given 12 hourly or 8 hourly. We have therefore evaluated the acute and sustained (2 weeks) effects of isosorbide-5-mononitrate 40 mg given twice daily (08.00 h and 14.00 h, allowing an 18-h dose-free period) in 19 patients with stable chronic angina, using computerized exercise testing and a placebo-controlled, double-blind, randomized trial protocol. There were two phases of 2 weeks each in which patients received placebo or active isosorbide-5-mononitrate. Acute testing was performed 2 h after the first dose and chronic testing 2 h after the morning dose on Day 14. Acute testing showed an increase in exercise time from a mean (SD) of 6.7 (2.2) min to 10.1 (2.95) min (P<0.01) after a single dose of isosorbide-5-mononitrate 40 mg. The time to 1 mm of ST depression, and rest and peak exercise heart rates increased significantly during acute testing with isosorbide-5-mononitrate; resting and peak exercise systolic blood pressures fell significantly. Due to drop outs cross-over analysis was performed on 11 patients who completed both chronic phases and 13 patients were assessed for the comparison of acute isosorbide-5-mononitrate with chronic isosorbide-5-mononitrate. After 2 weeks of therapy exercise time did not show a sustained increase 8.01 (2.14) min chronic placebo to 8.58 (1.93) min chronic isosorbide-5-mononitrate. The improvement in ST segment variables seen acutely was not sustained. These data suggest that the attenuation of the effect of isosorbide-5-mononitrate due to partial tolerance is not mitigated by using an asymmetrical dose regimen.     

Lack of correlation between exercise and sibenadet-induced changes in heart rate corrected measurement of the QT interval

AIMS: We sought to investigate subject specific QT interval correction factors (SSCF) determined at rest and after exercise and to determine the validity of these factors after the administration of a probe drug known to increase heart rate without directly affecting cardiac repolarization. METHODS: Thirty-two healthy volunteers underwent graded exercise, multiple recordings of electrocardiogram during rest over a day and a treatment phase administering inhaled placebo or sibenadet (a beta(2)-adrenoceptor/dopamine D(2)-receptor agonist) at 250, 500 or one of 750 or 1000 microg. SSCF were determined from linear regression of plots of log RR interval vs. log QT after exercise (QTcX), rest (QTcR), and combined data (QTcC). The SSCFs along with Bazett & Fridericia corrections were applied to the ECGs after inhalation of sibenadet. RESULTS: SSCFs obtained from the combination of the exercise and resting day (mean QTcC = 0.41) and exercise alone (mean QTcX = 0.40) were similar with a good fit to the data (mean r(2) = 0.92 and 0.93, respectively) while data at rest resulted in a less pronounced slope (mean QTcR = 0.27) and poorer fit (mean r(2) = 0.52). After the administration of sibenadet, none of the SSCFs, Bazett or Fridericia corrections adequately corrected QT for heart rate induced changes. CONCLUSIONS: Neither a SSCF from exercise, Bazett's or Fridericia's correction factors, adequately corrected the QT interval after the administration of a sympathomimetic agonist drug to increase heart rate in healthy volunteers demonstrating the potential need for QT/RR correction factors to be tailored for each drug studied.     

Continuous oral N-acetylcysteine treatment and development of nitrate tolerance in patients with stable angina pectoris.

The presence of sulfhydryl (SH) groups appears to be fundamental to nitrate-induced vasodilation and N-acetylcysteine (NAC), a sulfhydryl (SH)-donor substance, potentiates hemodynamic responsiveness to nitrates. We investigated the effect of simultaneous administration of NAC and isosorbide dinitrate (ISDN) on development of nitrate tolerance. In a double-blind, randomized, placebo-controlled cross-over study, seven patients with stable angina pectoris were treated for two 8-day periods with ISDN (40 mg four times daily, q.i.d.) together with NAC (controlled release 600 mg q.i.d.) or matching placebo. Bicycle exercise tests were performed before treatment was started, 1 h after treatment was started, and at day 8. After 8-day treatment with ISDN + placebo, responses determined by exercise testing were diminished as compared with responses obtained during acute therapy and did not differ from baseline values, suggesting development of tolerance to ISDN. During treatment with ISDN + NAC, time to 1-mm ST depression was significantly prolonged (441 +/- 44 vs. 381 +/- 40 s, mean +/- SEM) and total ST segment depression significantly reduced (1.9 +/- 0.7 vs. 3.5 +/- 0.8 mm) as compared with baseline values. The reduction in ST segment depression was significantly more pronounced during ISDN + NAC (46%) as compared with ISDN + placebo (23%). Although exercise time and time to angina pectoris were unaffected. NAC augmented the antiischemic effects of ISDN as assessed by ECG. This finding may suggest that development of nitrate tolerance is modified by chronic oral high-dose NAC administration.     

Cardiovascular and symptomatic reduction effects of alprazolam and imipramine in patients with panic disorder: results of a double-blind, placebo-controlled trial

Seventy-nine patients with panic disorder were randomized to an 8-week double-blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure.     

生长抑素对恶性肠梗阻患者免疫功能的影响

目的:探讨应用生长抑素(商品名思他宁)非手术治疗恶性肠梗阻患者免疫功能的变化及临床意义。方法:将70例非手术治疗的恶性肠梗阻患者分为研究组和观察组,每组35例。研究组给予思他宁治疗;观察组给予常规治疗。检测治疗后两组患者的细胞免疫指标(CD 4+,CD 8+及CD 4+/CD 8+)、体液免疫指标(IgMI,gA和IgG)以及血清免疫调节因子(IL-1I,L-6和TNF-α)的变化,并观察两组患者并发症发生率的变化。结果:两组患者治疗后10 d的检测结果显示,研究组CD4+及CD4+/CD8+值明显高于观察组(P<0.05);IgMI,gA和IgG值明显高于观察组(P<0.05);血清IL-1I,L-6和TNF-α的浓度明显低于观察组(P<0.05)。研究组并发症发生率明显低于观察组(P<0.05)。结论:恶性肠梗阻患者应用生长抑素治疗能明显改善临床症状,提高保守治疗的成功率,同时能明显改善机体免疫功能,降低并发症发生率,有利于患者的康复。     

Effect of ticlopidine on exercise-induced platelet aggregation and exercise tolerance time in patients with ischemic heart disease

Platelet aggregation is one of the most important mechanisms for acute myocardial infarction during exercise. We sought to evaluate the effect of ticlopidine (TP) on platelet aggregation (PA) during exercise in patients with ischemic heart disease (IHD). We studied 38 patients with IHD, 26 patients with effort angina pectoris, and 12 patients with a previous myocardial infarction. In protocol I, subjects were divided into two groups. Drugs altering platelet aggregation were withheld 2-4 weeks before the study in 25 patients (control group). TP (200 mg/day) was administered for 7 days in 13 patients (ticlopidine group). A symptom-limited modified Bruce protocol treadmill exercise test was performed. PA was measured at rest and after exercise by using optical densitometry induced by adenosine diphosphate (ADP). PA ratio (percentage of maximum) was compared. In protocol II, in 12 patients, treadmill exercise test and PA measurement were performed with and without TP. PA significantly increased after exercise in control (from 51.7+/-23.3% to 64.4+/-27.7%, p < 0.01) and ticlopidine (from 31.9+/-10.5% to 42.0+/-20.4%, p < .01) groups; however, its grade was lower in the ticlopidine group than in the control group. After exercise, PA was lower in the ticlopidine group than in control group (42.0+/-20.4% vs. 64.4+/-27.7%; p < 0.01). In the same patients, PA was lower with TP than without TP after exercise. Treadmill exercise-tolerance time was greater in the ticlopidine group than in the control group, but not statistically significant (762.3+/-139.2 vs. 711.6+/-169.6 s; NS). Exercise-tolerance time was significantly greater with TP than without TP in same patient (791.7+/-98.9 vs. 733.3+/-152.8 s; p < .05). TP suppressed the increase of PA during exercise and increased the exercise-tolerance time in patients with IHD.