Clinical and cardiovascular effects of alpha methyldopa in combination with decarboxylase inhibitors.

The peripheral decarboxylase inhibitor carbidopa, given (100 mg/day) for 6 wk in a double-blind trial, lowered supine diastolic pressure of 10 patients with essential hypertension treated with alpha methyldopa by a small (6 mm Hg) but significant (p less than 0.05) amount. Large doses of benserazide (1.5 gm) did not modify the hypotensive effect of 1.0 gm of alpha methyldopa in untreated hypertension but significantly reduced the central nervous side effects of sedation and dry mouth. These studies indicate that extensive peripheral decarboxylation is not necessary for alpha methyldopa to lower blood pressure and would be compatible with the central nervous site of hypotensive action of this drug.

Cardiovascular effects of a new inotropic drug in dog and normal man.

Cardiovascular effects of 1-butyl-3(1-(6,7-dimethoxyquinazolin-4-yl) piperidin 4 yl urea) (BDPU) were studied in 16 anesthetized dogs and in 7 healthy male volunteers. In animal experiments intravenous doses of 100, 250, and 500 mug/kg/min produced dose-related, significant increases in cardiac output and peak left ventricular dp/dt. No changes in heart rate and blood pressure occurred at 100 mug/kg/min, whereas higher doses caused falls in both systolic and diastolic blood pressures, accompanied by significant rises in heart rate. Inotropic effects could also be demonstrated in man. Changes of the systolic time intervals were dose-related and began at 64 mug/kg/min. At 250 mug/kg/min, the highest dose administered, the pre-ejection period decreased by 14.8 +/- 4.42 msec and its ratio with left ventricular ejection time by 0.049 +/- 0.017 against their respective control values (p less than 0.01). In contrast to animal experiments, no hypotension or tachycardia was observed in any subject. Pharmacokinetic studies showed a plasma elimination half-life of 76 +/- 3 min (mean +/- SE). There were no subjective side effects and standard laboratory tests were not altered, but there was a slight but significant rise in the urinary enzymes, lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT), which persisted up to 7 days.

Diagnosis of dissecting aortic aneurysm with suprasternal echocardiography.

A 33 year old woman with Marfan's syndrome and aortic root dissection was studied with precordial and suprasternal echocardiography. The precordial approach revealed some typical features of aortic root dissection. With suprasternal echocardiography it was possible to visualize the characteristic diagnostic feature of this disease: within the aortic lumen an m-shaped pattern--the aortic intimal flap--moving downward to the posterior aortic wall during systole. The diagnosis was confirmed with aortic cineangiography and intraoperative findings. Thus, suprasternal echocardiography can be a useful method of detecting aortic root dissection, especially in patients with aortic arch dissection alone.

Effects of cholestyramine on vitamin E levels in patients treated with statins.

The aim of this study was to investigate the effects of cholestyramine in combination with statins on vitamin E levels and their concentration related to LDL-cholesterol (LDL-C) in patients with hyperlipidemia. In an open-label, randomized study of 25 patients with elevated LDL-C, 12 received cholestyramine (12 g/d) in addition to chronic statin therapy, which had been started at least 8 weeks prior to the study in all patients. At the start and end of the 12-week study period, vitamin E concentrations were measured by high-performance liquid chromatography and cholesterol and triglycerides enzymatically in all patients. Vitamin E levels remained virtually unchanged within normal range before (11.90 +/- 0.71 mg/l) and after 12 weeks (11.69 +/- 0.82 mg/l) of concomitant therapy with cholestyramine. However, the ratio of vitamin E/LDL-C increased from 7.48 +/- 0.56 to 8.58 +/- 0.75 (x 10(-2)) (p < 0.09) in the cholestyramine group but not in the control group. LDL-C concentrations decreased from 162.00 +/- 5.98 to 144.33 +/- 12.48 mg/dl. The authors conclude that cholestyramine 12 g/d given for 12 weeks in addition to chronic statin therapy did not lower vitamin E levels in hyperlipemic patients. However, antioxidant status (vitamin E/LDL-C ratio) seems to be improved by a cholestyramine-associated LDL-C decrease.

Uremic cardiomyopathy: studies on cardiac function in the guinea pig.

The effects of creatinine (5.6-22.6 mg/100 ml), guanidinosuccinic acid (8.7-35.2 mg/100 ml) and of urea (60-600 mg/100 ml) on the mechanical function and oxygen consumption in isolated guinea pig hearts have been assessed. None of the parameters measured (dp/dt max, dp/dt min and Q O2) was significantly affected by creatinine or guanidinosuccinic acid. However, urea significantly reduced mechanical activity and caused a marked increase of oxygen consumption, indicating impairment of heart function expressed as a diminution of the ratio formula (see text). Pretreatment with creatinine and guanidinosuccinic acid did not alter the effect of norepinephrine on mechanical activity and oxygen consumption when compared with the effects of norepinephrine (1 X 10(-8) g/ml and 1 X 10(-7) g/ml) given alone. In contrast, urea pretreatment lowered the norepinephrine induced increase of left ventricular pressure rise/fall and of oxygen consumption. In addition, reduction of the increase in the ratio formula (see text): after urea perfusion indicates diminution of the "economic" effect of norepinephrine.

Preliminary evidence for the mechanism underlying the development of tolerance to prazosin in congestive heart failure: the alpha-agonistic properties of dobutamine unmasked by prazosin treatment.

The hemodynamic effects of acute and chronic treatment with different vasodilators were assessed in patients with chronic heart failure of New York Heart Association (NYHA) class III-IV. Each of 24 patients was randomly allocated; 6 to each of four groups: isosorbide dinitrate, dihydralazine, captopril, or prazosin. In addition, we evaluated the hemodynamic response to dobutamine by using increasing infusion rates of 2.5, 5.0, and 10.0 micrograms/kg/min at the start and end of a 3-month period of chronic therapy with either vasodilator. Dobutamine caused a dose-dependent increase in cardiac index and a decrease in mean pulmonary artery pressure (PAP) at the start of the vasodilatory treatment and maintained the effects during a 3-month period of chronic treatment with either isosorbide dinitrate, dihydralazine, or captopril. After 3-month therapy with 6 mg/day prazosin, however, mean PAP was increased above pretreatment value and dobutamine caused a further increase in PAP, thus reversing the initial effects. The dobutamine-induced increase in cardiac index remained virtually unchanged. We conclude that the reversal of the effects on PAP after chronic treatment with prazosin may be, at least in part, due to upregulation of alpha 1-adrenoceptors. This appears to be unmasked by the alpha 1-adrenoceptor agonist of the (-)-enantiomer of the racemic mixture of (+/-)-dobutamine.

Antihypertensive effects, plasma levels and beta-adrenergi blocking activity of racemic and dextrorotatory propranolol in man.

In hypertensive patients, whose blood pressure was decreased by racemic propranolol, the dextrorotatory isomer had no antihypertensive effect. The differences in antihypertensive activity of racemic and dextrorotatory propranolol cannot be explained by different plasma levels. The data indicate that the hypotensive effect of propranolol is due to beta-receptor blockade.

Site of action of methyldopa in lowering the blood pressure in man.

1. Methyldopa was administered to hypertensive patients in association with two different inhibitors of dopa decarboxylase, one of which, carbidopa, scarcely penetrates the central nervous system while the other, benserazide, penetrates the central nervous system when given in high doses. 2. The evidence suggests that in man, as in animals, the predominant action of methyldopa is mediated by the formation of methyldopamine and methyl-nor-adrenaline within the brain.

[Hemodynamic actions on alinidine during exercise in patients with coronary artery disease].

The effect of Alinidine (ST 567) on hemodynamics at rest and during exercise was studied in subjects with angiographically documented coronary artery disease and left ventricular dysfunction. Exercise tests were performed before and 30 min after intravenous administration of 20 mg of Alinidine. Significant decreases were observed for heart rate at rest and during exercise, for systolic and diastolic blood pressure. Pressures in the pulmonary artery and in capillary wedge position were significantly reduced after Alinidine by about 12 to 18% (mean PAP) and by about 19 to 28% (PCW). Cardiac output and stroke volume increased during exercise after Alinidine, but the differences were not significant. Depression of ST-segment in the exercise-ECG was significantly lower after Alinidine, angina pectoris occurred in all but one subject during control testing but in none after Alinidine. It is concluded that Alinidine is an effective antianginal drug. Intravenous administration of this agent even in a low dose improves cardiac performance during exercise in patients with impaired left ventricular function. Negative inotropic effects of Alinidine were not observed in this study. Bradycardia and in addition preload reduction are suggested to be the main mechanisms to improve left ventricular function and symptomatic status.

[Motion of the posterior wall in the m-mode echocardiogram - a parameter of global left function (author's transl)]. / Die Bewegung der Aortenhinterwand im M-mode-Echokardiogramm: Ein Parameter der linksventrikulären Funktion.

The cardiac output was determined by thermodilution in 42 patients during heart catheterization and compared to the amplitude of the posterior aortic wall in the m-mode echocardiogram. The amplitude of the posterior aortic wall was measured at the time of the closure of the aortic cusps (KS) and at the time the maximal excursion of the posterior aortic wall occurred (GA). Both parameters correlated strongly to the cardia output (r = 0.84, KS; r = 0.76, GA) and to the forward stroke volume (r = 0.81, KS; r = 0.73, GA). Thus, the amplitude of the posterior aortic wall in the m-mode echocardiogram is a useful parameter in predicting left ventricular function especially in those patients, in whom determination of left ventricular function from the m-mode echocardiogram is limited due to left ventricular asynergy.

A comparison of cardiovascular effects of dobutamine and isoprenaline after open heart surgery.

In a cross-over study, the cardiovascular effects of dobutamine were assessed in 11 patients who had undergone operation for replacement of the mitral or aortic valve approximately four hours earlier. In 9 of these the effects of isoprenaline were assessed for comparison. Dose-response curves were obtained using four dose levels of dobutamine in the range 1.25-10 mug/kg per min and of isoprenaline in the range of 0.005-0.04 mug/kg per min. Both drugs produced similar dose-dependent increases in heart rate and cardiac output and a dose-dependent decrease in peripheral resistance. Mean arterial pressure was only slightly increased by either drug. The positive inotropic effect of dobutamine was confirmed, but the chronotropic effect was not significantly different from that of isoprenaline. This contrasts with the findings of previous studies, and possible reasons for this are discussed.

[Fully automatic computer-analysis of electrocardiograms in clinical routine (author's transl)]. / Vollautomatische, rechnergestützte Befundung von Elektrokardiogrammen im Routineeinsatz.

A fully automated Ecg recording and interpretation system (Hewlett Packard HP 5) consisting of a central computer and two peripheral units was evaluated during a four-month period. Ecgs were transmitted via public telephone lines, as was the report from central station to peripheral recording and print-out unit. Within a few seconds after recording and print-out unit. Within a few seconds after recording and transmission a preliminary report is available in printed format. The transmitted Ecgs are stored at the central computer and are being retrieved and evaluated manually there. Three cardiologists read the tracings and furnished final reports. 468 Ecgs were thus compared in our test time of 10 days for statistical evaluation with the following results: 1. 73.1% of all statements were read correctly by the computer. 2. There is a large range of diagnostic accuracy between 0% and 100%. 3. The evaluation of Ecg changed by cardiologists reflects the individual experience of the controllers regarding the Ecg statements as well as computer-dependent possibilities like modification etc. of Ecg. 4. As an example the diagnosis "myocardial infarction" is compared with other Ecg computer programs by means of a quality index calculated from sensitivity and specificity: HP 5 with 158.5 points reaches a similar level as the Pipberger program with 162.6 and the Bonner with 159.5 points. 5. Referring to false negative results this program is acceptable in all diagnostic groups with ca. 8%, except conduction defects with 17.7%. 6. Referring to false positive results the diagnostic groups myocardial infarction/ischemia and conduction defects are not satisfactory with 36.5% and 23.4%. 7. In all the tested system seems to be very useful in routine Ecg interpretation of bigger hospitals.

Electrophysiological actions of lorcainide in patients with cardiac disease.

Lorcainide is a new antiarrhythmic agent which effectively suppresses ventricular premature contractions. Its electrophysiological actions were studied in 15 cardiac patients with and without cardiac conduction abnormalities. In a dose of 2 mg/kg body weight, lorcainide decreased the sinus cycle length (SCL) and increased the corrected sinus node recovery time. The intra-atrial, atrioventricular (AV), and intraventricular conduction times were prolonged. A third-degree AV block developed in 2 patients with pre-existing conduction abnormalities. QRS widening showed that intramyocardial conduction was also affected. The effective refractory period of the atrioventricular node (ERP-AVN) was shortened, whereas the effect on the functional refractory period of the AVN was variable. The decrease in SCL and ERP-AVN may be due to a possible anticholinergic effect of the drug. The accessory pathway was blocked in 3 patients with a Wolff-Parkinson-White syndrome. The ERP of the ventricle was slightly prolonged. The electrophysiological profile of the drug, i.e., slowing of conduction velocity throughout the heart combined with shortening of SCL and ERP-AVN, differs from other antiarrhythmic agents.