Reduction of creatine kinase and creatine kinase-MB indexes of infarct size by intravenous verapamil.

In a prospective, controlled study, 29 patients were randomly allocated to receive intravenous verapamil, 5 to 10 mg/hour, for 2 days starting at a mean of 8 hours after the onset of myocardial infarction. Twenty-five patients received no specific treatment and served as control subjects. Left ventricular (LV) filling pressure in all patients was initially less than 15 mm Hg. Age, infarct localization and hemodynamic values on admission (Swan-Ganz catheter) were comparable in both groups. Maximal creatine kinase (CK) and creatine kinase-MB (CK-MB) values were markedly lower in the verapamil group than in the control group (CK 547 vs 703 U/liter, p less than 0.05; CK-MB 51 vs 68 U/liter, p less than 0.025), as was infarct weight (48 vs 65 g-Eq, p less than 0.03; CK-MB 31 vs 49 g-Eq, p less than 0.005). Arterial blood pressure was 10% lower in the verapamil group than in the control group. Systemic vascular resistance and LV filling pressure remained unchanged. Verapamil reduced myocardial infarction size by about 30% in patients without LV failure and the arterial pressure was reduced.

Orally administered isosorbide dinitrate in patients with and without left ventricular failure due to acute myocardial infarction.

The oral effectiveness of 10 mg followed by 20 mg of isosorbide dinitrate in 21 patients with acute mycardial infarction was studied over a period of 13 hours. The patients were grouped according to initial left ventricular filling pressure: group I, pressure less than 20 mm Hg, and group II, pressure more than 20 mm Hg. Patients in group II had left ventricular failure. In both groups isosorbide dinitrate resulted in a significant decrease in pulmonary arterial pressure. The left ventricular filling pressure decreased in group I from 13.6 +/- 4.0 to 7.1 +/- 2.6 mm Hg (mean +/- 1 standard deviation) and in group II from 26.9 +/- 4.6 to 19.0 +/- 3.6 mm Hg (P less than 0.001). Cardiac output decreased in group I from 5.1 +/- 1.0 to 4.5 +/- 0.9 liters/min, whereas in group II it increased significantly from 3.5 +/- 0.8 to 4.1 to 0.9 liters/min (P less than 0.001). In both groups, peripheral arterial blood pressure decreased (P less than 0.60). Heart rate remained constant. Whether cardiac output increased or decreased was found to be dependent on the initial left ventricular filling pressure. In patients with an initially high value (above 20 mm Hg), the increase in cardiac output is probably due to the reduction of afterload. An additional factor may be the decrease in left ventricular filling pressure, which leads to an improved blood supply in the affected mural segments as a result of the decrease in the extravascular component of the coronary resistance. Significant changes in cardiac output and left ventricular filling pressure were achieved 3 to 5 hours after oral administration of isosorbide dinitrate. Clinical signs of failure were less pronounced. Isosorbide dinitrate is, therefore, a therapeutic agent in the treatment of left ventricular failure due to acute myocardial infarction.

Dose-response relation of antianginal activity of isosorbide dinitrate.

Eleven men with angiographic evidence of coronary heart disease and stable, exercise-induced angina pectoris were given placebo (P) or isosorbide dinitrate (ISDN) in a daily dose of 30, 120, 240 or 480 mg, in a randomized single-blind trial. The daily doses were administered 6 times a day as single oral doses of 5, 20, 40 and 80 mg. Each dose or placebo was given for 7 days. Before therapy was begun, and on the seventh day of each treatment period, an exercise ECG with standardized level and duration of exercise was recorded. Subsequently, a 4-week treatment period with 480 mg/day was carried out at the end of which another stress test was performed. The was followed by a final 2-week placebo period. The frequency of anginal attacks per week tended to decrease with increasing nitrate doses, but decreased significantly only after the highest dose (480 mg/day) compared with placebo. Continuation of therapy with 480 mg/day maintained the reduced rate of anginal attacks. The ischemic response, expressed as the sum of ST-segment depressions in the exercise ECG, revealed a dose-dependent reduction of 26% (30 mg/day), 39% (120 mg/day) (p less than 0.01), 63% (240 mg/day) (p less than 0.01) and 72% (480 mg/day) (p less than 0.01), respectively. At the end of the 4-week treatment period with 480 mg/day, antianginal efficacy was found to be moderately reduced, showing a 56% reduction of ischemic response compared to the placebo trial. The time of onset of angina during exercise testing was also delayed in relation to the dosage given.(ABSTRACT TRUNCATED AT 250 WORDS)

The Frankfurt experience in restenosis after coronary angioplasty.

Three hundred and thirty-three of 356 patients underwent angiographic follow-up from 1 to 18 months (mean 5.6 months) after percutaneous transluminal coronary angioplasty (PTCA). This is a reangiography rate of 94%. Recurrence rate after the first PTCA was 15% (n = 289). Restenosis rate was defined as an increase from immediate post-PTCA stenosis of more than 30%, or the loss of at least half of the initial gain in luminal diameter. Patients who needed a second angioplasty due to restenosis (n = 30) had a restenosis rate of 33%. Patients with angioplasty in the aortocoronary bypass (n = 14) had a restenosis rate of 45%. All patients were treated before, during and at least 4 to 6 months after the procedure with 60 to 100 mg of isosorbide dinitrate daily plus 160 to 360 mg of verapamil or 100 to 150 mg of gallopamil and 1.5 g of acetylsalicylic acid. In a second retrospective study 111 of 399 patients had the acetylsalicylic acid therapy discontinued or decreased. Forty-two of them developed restenosis (38%), whereas only 49 of 288 patients who continued to receive 1.5 g aspirin developed restenosis (17%). The restenosis rate was 32% in those who received the reduced dose of aspirin. Thus, a large dose of acetylsalicylic acid given before, during and 4 to 6 months after the procedure seems to be necessary to achieve a low rate of restenosis after PTCA.

Restenosis is a common feature of the angiographic follow-up after balloon valvoplasty of calcified aortic stenoses.

Balloon dilatation of calcified aortic stenosis was attempted in 12 patients, 6 men and 6 women, aged 38-82 years. Two patients underwent emergency surgery because of myocardial injury or pericardial tamponade. One patient with severe depressed left ventricular function in whom the procedure was attempted in cardiogenic shock died during the procedure. One patient experienced severe aortic insufficiency after dilatation. The remaining pressure gradient was higher than 50 mm Hg in another patient. Seven dilatations were considered to be successful with a remaining pressure gradient below 50 mm Hg and a mean gradient reduction of 53 mm Hg. In one of these 7 patients, who suffered from severe heart failure, valvoplasty had been carried out to make aortic valve replacement possible. The operation was performed 2 weeks later without complications. Five of 6 patients treated medically after successful valvoplasty had restenosis within 3 to 12 months. One of them exhibited a good result at 3 months but severe restenosis after one year. It is concluded that balloon valvoplasty of calcified aortic stenosis cannot be considered an alternative to surgery. If, however, left ventricular function improves after successful valvoplasty, valve replacement will then carry less risk.

First dose hypotension with enalapril and prazosin in congestive heart failure.

Since the introduction of angiotensin converting enzyme inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the angiotensin converting enzyme inhibitor enalapril a multicenter, open, randomized, prazosin-controlled trial was designed comparing the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 mg prazosin. Subjects were 1210 inpatients with New York Heart Association functional class (I)/II and III who were not adequately compensated with digitalis and/or diuretics. In the group receiving enalapril, 3 patients (0.5%) experienced severe hypotension on day 1 and 28 patients (4.7%) moderate hypotension. In those given prazosin, 15 patients (2.6%) experienced severe hypotension and 60 patients (10.3%) moderate hypotension. The difference is statistically significant (P less than or equal to 0.000012). All patients recovered. It was concluded that treatment of patients suffering from congestive heart failure New York Heart Association functional class (I)/II or III with enalapril is comparably well tolerated.

[Nuclear medicine in determining the shunt in ductus arteriosus Botalli]. / Nuklearmedizinische Shunt-Bestimmung beim Ductus arteriosus Botalli.

In 9 patients with patent ductus arteriosus, quantification of left-to-right shunt was performed with dye dilution curves after peripheral injection and with radionuclide ventriculography. The study was repeated within 7 days after successful transluminal occlusion of the ductus with an Ivalon-plug. Reproducubility of the method could be studied in one patient in whom reopening of the ductus occurred. Dye dilution curves were analyzed using the method of Carter et al. Radionuclide ventriculography was performed as a combined first-pass and equilibrium study: effective stroke volume was derived from the first pass of the tracer through the heart; during the equilibrium phase left ventricular ejection fraction (EF) and left ventricular enddiastolic volume (EDV) were evaluated. The difference between total left ventricular stroke volume (product of EF and EDV) and effective stroke volume was taken as shunt volume. This volume as a fraction of total left ventricular stroke volume resulted in percent left-to-right shunt. The sensitivity of the dye technique was 78%; a quantification of the shunt lesion was possible in 55% of all cases (shunt greater than 35%). The sensitivity of the radionuclide technique was 90%. The severity of the lesion could not be determined in one patient with a minimal shunt. After successful occlusion of the ductus, dye dilution curves normalized in all cases. Radionuclide ventriculography showed normalization in all but one patient. This patient with concomitant mitral regurgitation still showed moderate left ventricular volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled study of intravenous nitroglycerin treatment for two days in patients with recent myocardial infarction.

Hemodynamic measurements were obtained for 48 h in 46 patients with recent myocardial infarction. Patients were randomized to treatment with (n = 22) and without nitroglycerin (NTG) n = 24). In patients with diastolic pulmonary arterial pressure (PAEDP) less than 20 mmHg (group I), NTG decreased PAEDP from 15 to 11 mmHg (n = 13); in the untreated control group PAEDP remained unchanged (n = 15). Cardiac output decreased in the NTG group from 5.4 to 5.0 1/min and in the control group from 4.7 to 4.4 1/min. Mean arterial pressure decreased in both groups, in the NTG group from 106 to 97 mmHg and in the control group from 102 to 94 mmHg. In patients with left ventricular failure and PAEDP greater than 20 mmHg (group II) the decrease in left ventricular filling pressure was significantly greater (25 to 17 mmHg, n = 9) than in the control group (24 to 20 mmHg, n = 9). Cardiac output increased during NTG treatment from 4.2 to 5.1 1/min. In the control group, however, cardiac output decreased from 4.2 to 3.6 1/min. Mean arterial pressure decreased from 103 to 95 mmHg in the NTG group and from 114 to 96 mmHg in the control group. Heart rate did not change significantly. Thus, PAEDP decreased significantly in patients who received NTG treatment for 48 h compared to an untreated control group. Cardiac output increased in treated patients, especially those with left ventricular failure, but decreased in the control group. Mean arterial pressure decreased to the same degree in treated patients and in controls.

Nitroglycerin in acute myocardial infarction. X. Effect of small and large doses of nitroglycerin on sigma ST segment deviation -- experimental and clinical results.

The purpose of the present study was to investigate the effect of the dose of nitroglycerin (NTG) on myocardial ischemic injury. In 20 closed chest dogs the anterior descending branch of the left coronary artery was occluded by inflating a balloon in its lumen. Compared with the untreated control group the sigma ST elevation was significantly lower when NTG was applied at a rate of 0.02 mg/min, but significantly higher when NTG was administered at a rate of 0.10 mg/min. In 12 patients with acute myocardial infarction NTG was infused at a rate of 3 mg in the first hour (0.05 mg/min) and 6 mg in the second hour (0.1 mg/min). Sigma ST elevation and sigma ST depression decreased during the lower infusion rate (p less than 0.001). When the rate of NTG infusion was raised to 6 mg/hr, the improvement in ST segment deviation was partially reversed. This effect, particularly evident in patients not in heart failure, was associated with a significant rise in heart rate (p less than 0.05) and a fall in diastolic arterial pressure (p less than 0.025). Patients with left ventricular failure were less sensitive to higher doses of NTG than those without failure. Thus, the effect of NTG on myocardial ischemic injury depends on the NTG dose and on the functional state of the injured left ventricle.

Captopril in acute myocardial infarction: beneficial effects on infarct size and arrhythmias.

It is known from experiments that angiotensin-converting enzyme inhibitors can limit infarct size. In a prospective, randomized, placebo-controlled double-blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 and 18 h from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With the exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV, p < 0.05). The number of ventricular premature beats at 24 h from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred seven times in the placebo group, but did not occur in the captopril group. The creatine kinase infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). Mean arterial pressure was reduced by 12 mmHg with captopril treatment. The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

Double-blind randomized multicenter study on the efficacy of trapidil versus isosorbide dinitrate in stable angina pectoris.

BACKGROUND: Trapidil is an inhibitor of phosphodiesterase I-IV with resulting positive lusitropic, vasodilating, and antiplatelet effects. HYPOTHESIS: This study was undertaken to compare the antianginal efficacy of trapidil with that of isosorbide dinitrate (ISDN) in patients with stable angina pectoris. METHODS: We studied 95 patients with stable angina pectoris who were randomized into a double-blind parallel group study with either oral trapidil or ISDN. After a 1-week run-in period and a 2-week wash-out phase, the patients received either trapidil 200 mg t.i.d. (n = 48) or ISDN 20 mg t.i.d. (n = 47) for 12 weeks. All antianginal medication, except sublingual glyceryl trinitrate (GTN), was discontinued during the study. Patients underwent an exercise electrocardiogram on an ergometer bicycle according to a modified Bruce protocol before and at 6 and 12 weeks during treatment. RESULTS: The workload capacity increased from 583 +/- 281 W.min before treatment to 833 +/- 444 W.min after 12 weeks of treatment in the trapidil group (p < 0.01) and from 555 +/- 276 W.min to 827 +/- 361 W.min in the ISDN group (p < 0.01). The anginal attacks per week as well as the use of GTN decreased significantly in both groups. After 12 weeks of therapy, the cumulative ST-segment depression during exercise decreased by 67% in the trapidil patients and by 23% in the ISDN patients. Compared with baseline, the double product at the 75 W level was reduced in both groups after 12 weeks of treatment. Blood pressure and heart rate at rest remained nearly unchanged. Overall, no statistical difference was found between the two study groups. The tolerability was good. CONCLUSION: Oral trapidil therapy is safe and effective in stable angina pectoris and is equivalent to standard therapy with ISDN.

[Renal artery dilatation in renovascular hypertension. Acute and long-term outcome in a large patient sample]. / Nierenarteriendilatation bei renovaskulärer Hypertonie. Akut- und Langzeitergebnisse eines grossen Patientenkollektivs.

BACKGROUND: Renal angioplasty is an established therapy for treatment of renovascular hypertension. This study was performed to evaluate short- and long-term outcome of this procedure up until 3 years afterwards. PATIENTS AND METHODS: Altogether, 111 renal artery stenosis in 92 patients were dilated. Among these were 31 fibromuscular and 70 arteriosclerotic lesions, 4 transplant artery stenosis and 6 occlusions. RESULTS: The primary success rate for dilatation was approximately 90%. Serious complications occurred in 5 of the patients including 2 fatal myocardial infarctions about 2 weeks after the procedure. Restenosis (altogether 25%) almost exclusively occurred during the first few months after angioplasty (more often in arteriosclerotic lesions than in fibromuscular disease). Successful dilatation resulted in better blood pressure control. In several patients with preexisting chronic renal failure improvement of renal function was observed; in this group, however, restenosis occurred in about 1 third of the patients. CONCLUSIONS: Renal angioplasty is a suitable method for therapy of renovascular hypertension; in patients with preexisting renal failure improvement of renal function may ensue. The decision to treat with angioplasty must be weighted carefully against other established and also newer methods (surgery vs. antihypertensive medication vs. stent implantation) and should be reserved for specialized centers.

Captopril in acute myocardial infarction. Beneficial effects on infarct size and arrhythmias.

OBJECTIVE: It is known from experiments that angiotensin converting enzyme (ACE) inhibitors can limit infarct size. We examined the effect in patients. METHODS: In a prospective, randomized, placebo-controlled double blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 hours and 18 hours from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. RESULTS: The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV) (p < 0.05). The number of ventricular premature beats at 24 hours from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred 7 times in the placebo group, but did not occur in the captopril group. The creatine kinase (CK) infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). The mean arterial pressure was reduced by 12 mmHg with captopril treatment. CONCLUSIONS: The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

[Therapy with nitrates in the post-infarct phase]. / Therapie mit Nitraten in der Postinfarktphase.

The beneficial effects of nitrates in patients with angina pectoris and acute myocardial infarction have positively influenced the prognosis of the treated patients. Studies of Jugdutt pointed out that there is a better prognosis also in the postinfarction period. Especially left ventricular over dilatation, which follows larger infarct, can be prevented by a consistent nitrate therapy.