Wulf-Dirk Bussmann

Effect of sublingual nitroglycerin in emergency treatment of severe pulmonary edema

Abstract Twenty-two patients with clinical signs of pulmonary edema (orthopnea, cyanosis, profuse sweating and pulmonary rales∗) were studied and separated into two groups. In seven patients (Group A), hemodynamic studies were performed. Pulmonary arterial pressure and cardiac output were measured during the emergency condition of severe pulmonary edema. Within 10 minutes after sublingual administration of nitroglycerin, 1.6 mg, left ventricular filling pressure decreased from 33 ± 10 (mean ± 1 standard deviation) to 24 ± 8 mm Hg, and cardiac output increased significantly from 3.3 ± 0.8 to 3.7 ± 0.8 liters/min. In one patient with recent myocardial infarction, left ventricular filling pressure decreased from 50 to 27 mm Hg within 5 minutes. Orthopnea and pulmonary rales disappeared rapidly. In 15 patients (Group B), the clinical course was observed and documented. These patients received one to six doses of 0.8 to 2.4 mg of nitroglycerin sublingually at intervals of 5 to 10 minutes. Five minutes after administration, the first evidence of clinical improvement was observed in seven of these patients. After 15 to 20 minutes, pulmonary rales disappeared or decreased in 11 and dyspnea decreased in 14. The elevated arterial blood pressure and heart rate decreased significantly. Only one patient with terminal pulmonary edema remained refractory to therapy. Thus, sublingual nitroglycerin had beneficial effects in the emergency treatment of classic pulmonary edema. Elevated left ventricular filling pressure decreased and cardiac output increased within 5 minutes. These hemodynamic changes produced immediate clinical improvement.

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.

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.

Comparison of nitroglycerin with nifedipine in patients with hypertensive crisis or severe hypertension

SummaryTo determine whether nitroglycerin is as effective as nifedipine in lowering the blood pressure in severe hypertension and hypertensive crisis, two goups of 20 patients received in random sequence either 1.2 mg nitroglycerin sublingually or a 10-mg nifedipine capsule, which was chewed and swallowed. The blood pressure fell after 5 min in the nitroglycerin group from 211/122 mmHg to 171/95 mmHG and after nifedipine from 210/118 to 185/102 mmHg. The greater effect of nitroglycerine may result from faster absorption through the oral mucosa than through the small intestinal mucosa where nifedipine is primarily absorbed. After 15–20 min a satisfactory reduction in blood pressure was reached in both groups: 157/91 and 158/92 mmHg, respectively. After 30 min the heart rate in the nitroglycerin group had decreased from 83 to 80/min, but in the nifedipine group it had increased from 84 to 90/min. The reduction in blood pressure persisted up to 6 h. No significant differences in side effects were determined. Since a hypertensive crisis is usually accompanied by left ventricular failure, pulmonary edema, angina pectoris, or infarction, nitroglycerin has been definitively shown positively to influence these conditions, and preference should be given to nitroglycerin in the treatment of hypertensive crises.

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.

Ventricular Function at Rest, During Leg Raising and Physical Exercise Before and After Aortocoronary Bypass Surgery

In nine patients with coronary heart disease isometric contractility indices and ejection phase parameters were measured simultaneously using an angiographic catheter with a manometer at the tip (MILLAR). Regional wall motion at rest, after leg raising, and during physical exercise (bicycle ergometer) was analyzed applying the hemiaxis method. Five weeks after aortocoronary bypass surgery these examinations were repeated.

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)

Orally administered prajmalium bitartrate in acute and chronic ventricular arrhythmias

Abstract The effect of orally administered prajmalium bitartrate on premature ventricular complexes and on runs of such complexes was studied in 42 patients. Ventricular extrasystoles were quantified from stored continuous electrocardiographic tape recordings using a semiautomated arrhythmia-detection system. In 19 patients prajmalium bitartrate was given at a dose of 80 mg/24 hours (20 mg every 6 hours). Premature ventricular contractions decreased significantly. Two hours after administration of the drug, the frequency of premature ventricular complexes was reduced to 63 percent of the intial rate. After 6 hours the full drug effect was attained. After 12 hours the number of premature ventricular complexes averaged 30 percent of the initial value. During the succeeding drug-free interval the frequency of premature ventricular complexes increased and reached 57 percent of the initial value after 10 hours. In a second group of 14 patients each patient was treated with prajmalium bitartrate and procainamide (3 g/24 hours) for comparison of drug effects. No significant differences were found in the antiarrhythmic action of the two drugs. Prajmalium bitartrate was well tolerated by all patients. However, three patients receiving procainamide complained of nausea and gastrointestinal symptoms and two of them had to discontinue therapy. One patient receiving long-term procainamide therapy experienced reversible joint pains of a lupus erythematosus-like syndrome. In a third group of 23 patients with acute myocardial infarction 9 patients were given prajmalium bitartrate, 20 mg 3 times every 4 hours; 14 patients (control group) received no antiarrhythmic drug. In the control group premature ventricular complexes increased continuously up to the 10th hour after infarction and slowly decreased thereafter. Prajmalium bitartrate reduced the rate of premature ventricular complexes significantly to a mean of 4 percent of the initial value. In the untreated patients the rate decreased only to 60 percent of the initial value. Runs of premature ventricular complexes were suppressed immediately after administration of prajmalium bitartrate, whereas in the control group the frequency of such runs ranged between 80 and 140 percent of the initial value. These findings document the effective antiarrhythmic action of orally administered prajmalium bitartrate on premature ventricular complexes.

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.

Effects of intravenous nitroglycerin on ventricular ectopic beats in acute myocardial infarction

Ventricular premature beats (VPBs) in 21 consecutive patients with acute myocardial infarction (AMI) were continuously recorded on magnetic tape by means of an automatic arrhythmia monitor and counted manually. The patients were sequentially assigned to either a control (n = 11) or nitroglycerin group (n = 10). Both groups were comparable for age as well as for onset, localization, and extension of infarction. Recording in the control groups was begun at a mean of 9.3 hours following onset of infarction as obtained from patient history. This interval was 12.0 hours in the nitroglycerin group. At the start of therapy, the number of VPBs was identical in both groups. Ten patients received a mean of 2.1 mg of nitroglycerin per hour intravenously for 48 hours, whereas the control group received no specific therapy. The number of VPBs in the control group increased progressively until the sixth hour of registration and reached a maximum of 165% of the baseline value before subsequently declining. Nitroglycerin administration was associated with a significantly more rapid reduction in ventricular arrhythmias: 6 hours after onset of recording, the number of VPBs had declined to 39% of the baseline value (p less than 0.05 compared to control group). This study demonstrates that nitroglycerin reduces ventricular ectopic beats in the acute phase of myocardial infarction.