Friedrich Kersting

Echocardiography in assessing acute pulmonary hypertension due to pulmonary embolism

Eighteen patients with acute pulmonary embolism were studied with right heart catheterization and M mode echocardiography. No patient had evidence of preexisting cardiopulmonary disease; pulmonary embolism was documented with pulmonary angiography. The mean pulmonary arterial pressure correlated with the angiographic severity index of embolic obstruction (r = 0.61, p 2 , p 2 ) and in 5 patients with acute pulmonary embolism and a mean normal pulmonary arterial pressure (10.9 ± 0.4 mm/m 2 ). For all measurements the index size of the right pulmonary artery correlated with the mean pulmonary arterial pressure (r = 0.84, p

Lorcainide. II. Plasma concentration-effect relationship.

The effects of lorcainide were studied in 17 patients after single doses (2 mg/kg intravenously; 6 mg/min intravenously over 30 to 40 min; 150, 300, and 500 mg orally) and during long‐term antiarrhythmic treatment (200 to 600 mg daily orally). The frequency of ventricular premature contractions (VPCs), the changes in the electrocardiogram (ECG), and the plasma concentration of lorcainide were determined. The widening of the QRS complex observed after single doses of lorcainide mimicked the time course of plasma concentration permitting the construction of linear relationships between both parameters. After oral administration lower plasma concentrations were required to produce the same QRS widening than after intravenous administration. Patients differed considerably in the slopes of these plasma concentration‐effect curves. After repeated intravenous infusions of lorcainide, plasma concentration‐effect relationships were constructed for both antiarrhythmic and ECG effects. During drug infusion higher concentrations of lorcainide were required to induce antiarrhythmic and toxic effects (QRS widening and PQ prolongation) than during the postinfusion period. Whereas during the infusion period the plasma concentration‐effect curves for both effects followed the same slope, during the postinfusion period VPCs were remarkably more sensitive to plasma concentration than the changes in the ECG. Suppression of VPCs during long‐term treatment with lorcainide was accompanied by small changes in the ECG which were related to the dose and plasma concentration of lorcainide. Thus, the lorcainide regimen may be monitored by careful inspection of the ECG.

Lorcainide. I. Saturable presystemic elimination.

The disposition of lorcainide after single oral and intravenous doses and during long‐term oral and intravenous dosing was investigated in 17 patients with chronic ventricular premature contractions. Lorcainide is thought to be eliminated mainly by metabolism in the liver. After a single intravenous (IV) dose of 2 mg/kg, the mean systemic clearance was 1.67 1/min, which is equal to the normal liver blood flow rate. When 10 of these patients were treated with 2 different single oral doses, the fraction of the dose reaching the systemic circulation (F) rose from a mean of 0.27 to 0.50 when the dose was increased from 150 to 300 mg. After long‐term oral dosing F increased further and approached unity in some patients. The plasma concentration of the N‐dealkylated metabolite rose and exceeded that of the parent drug when long‐term IV treatment was replaced by long‐term oral treatment. Simultaneous measurements of plasma concentration of lorcainide in the abdominal aorta and hepatic vein in 2 patients showed a high hepatic lorcainide uptake after a single IV dose. When 1 of these 2 patients was treated orally for 3 days (3 × 100 mg/day) concentration differences in afferent and efferent liver blood disappeared. Lung did not extract measurable amounts of lorcainide in 2 patients, in whom the plasma lorcainide concentrations were measured in the pulmonary artery and thoracic aorta over a period of 30 min after a single IV dose of 2 mg/kg. Our results suggest that lorcainide is subject to saturable presystemic elimination, most likely due to a saturation of hepatic extraction.

Hemodynamic response to graded water immersion.

SummaryHemodynamic response to graded immersion was studied in healthy male subjects in a thermoneutral bath in the sitting position. Pressures in the right heart and cardiac output were determined by means of a semifloating catheter with a thermistor probe. Pressures in the right atrium, pulmonary artery and in pulmonary wedge position increased with increasing depth of immersion, cardiac output was likewise augmented. Heart rate decreased from rest to hip immersion but remained constant from hip to head out water immersion. Plasma norepinephrine concentration remained constant throughout the experiment. The reported changes depend on the blood shift from capacitance vessels into the thoracic cavity. From this, preload increased and cardiac performance was improved. However, in patients with disturbed left ventricular function, immersion to the neck may be potentially hazardous due to augmented left ventricular filling pressure.ZusammenfassungBei gesunden männlichen Probanden wurde das Verhalten hämodynamischer Parameter während stufenweise ansteigender Immersion in thermoindifferentem Wasser in sitzender Position untersucht. Das Herzzeitvolumen und die Drücke im rechten Herzen wurden mittels eines Swan-Ganz-Thermistorkatheters bestimmt. Mit ansteigender Immersionstiefe steigen die Drücke im rechten Vorhof, in der Pulmonalarterie und im Pulmonalkapillarbereich signifikant an, das Herzminutenvolumen nahm mit ansteigender Immersionstiefe zu. Die Herzfrequenz nahm bei Immersion bis zur Hüfte im Vergleich zu den Ruhewerten signifikant ab, blieb dann aber bei zunehmender Immersionstiefe unverändert. Die Plasmakatecholamine änderten sich während der verschiedenen Immersionsphasen nicht. Die beschriebenen Änderungen beruhen auf einer Blutumverteilung infolge des hydrostatischen Druckes auf die untere Körperhälfte. Das Blut wird aus den Venen der unteren Extremitäten und dem Abdomen in den Thorax verlagert. Hierdurch kommt es zu einer erheblichen Vorlastzunahme. Bei gleichzeitigem Anstieg des Herzminutenvolumens wird der Arbeitspunkt auf der linksventrikulären Funktionskurve nach rechts und oben verschoben, bleibt aber im Normbereich. Es ist anzunehmen, daß bei Patienten mit gestörter linksventrikulärer Funktion Immersion bis zum Hals (z.B. Schwimmen, Tauchen) zu einer Gefährdung führen kann.

Diagnosis of dissecting aortic aneurysm with suprasternal echocardiography

A 33 year old woman with Marfans 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.

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.

Haemodynamic effects of a single intravenous dose of lorcainide in patients with heart disease

SummaryThe cardiovascular effects of a single i.v. dose (2 mg/kg over 5 min) of lorcainide were studied in 14 patients with heart disease. In the haemodynamic part of the study (6 patients), the aortic and pulmonary systolic, diastolic and mean pressures, left ventricular systolic and end-diastolic pressures, cardiac output and the rate of rise of left ventricular pressure were measured before and for 30 min after administration of the drug. Lorcainide produced a slight and short-lasting decrease in the aortic and pulmonary systolic pressures, and all other pressure values remained unchanged. The cardiac output and systemic vascular resistance were not altered by lorcainide. It consistently depressed the rate of rise of left ventricular pressure (maximum mean decrease 19%). In the angiographic part of the study (8 patients), the ejection fraction and the mean velocity of circumferential fiber shortening were measured before and 5 min after lorcainide. In all but one patient, lorcainide decreased the ejection fraction (mean decrease 11.6%), and the mean velocity of circumferential fiber shortening was uniformly diminished by lorcainide (mean decrease 29.7%). Thus, lorcainide moderately impaired myocardial performance in patients with normal and reduced left ventricular function without producing hypotensive side effects.

Clinical electrophysiological properties of N-allyl-clonidine (ST 567) in man.

Summary: The electrophysiological properties of N-allyl-clonidine (ST 567) were studied in 18 patients. Four of these patients were pretreated with intra venous propranolol. 0.2 mg/kg, and atropine, 0.04 mg/kg, to induce autonomic blockade. ST 567 produces a sustained bradycardiac effect at a dose of 40 mg, i.v., in patients without (group I) and with (group II) autonomic blockade. The mean increase in Group I was 23% and in group II. 42%. The sinus node recovery time increased in both groups, from 1.151 ± 73 to 1,310 ± 81 msec in group I. and from 995 ± 145 to 1.599 ± 248 msec (means ± SEM) in group II. The corrected sinus node recovery time was unaffected by ST 567 in group I and increased from 165 ± 50 to 427 ± 117 msec in group II. The sinoartrial conduction time was unaffected by ST 567 in group I. The effective refractory period of the right atrium, the atrioventricular node and the right ventricle, as well as the functional refractory period of the atrioventricular node, were unaffected by ST 567 in patients without autonomic blockade. Intra-atrial, atrioventricular, and intravetricular conduction were also not altered by this drug. Thus, the electrophysiological profile of ST 567 differs from other bradycardia-inducing agents such as β-blockers or calcium antagonists.

Clinical Pharmacology of Prazosin and Phentolamine in Patients with Heart Failure

&NA; In a controlled crossover study we assessed the effects of an initial single oral dose of 150 mg phentolamine or 2 mg prazosin on the haemodynamics and plasma concentrations of noradrenaline in 12 patients with mild to moderate cardiac dysfunction in cardiomyopathy (NYHA Classes I‐III). Nine of these patients continued chronic oral treatment with either 300‐450 mg phentolamine or 7.5‐15 mg prazosin for a period of 4‐6 weeks each in randomised order. The effects on both haemodynamics and plasma noradrenaline were essentially the same under the treatment with both drugs. The acute effect on reduction of exercise‐induced elevation of diastolic pulmonary artery pressure was abolished after chronic treatment. However, significant increase in stroke volume—on average, from 83 ± 7.2 to 100 ± 6.0 ml (phentolamine) and 99 ± 6.7 ml (prazosin)—occurred only after chronic treatment. Increased sympathetic activity, as expressed in plasma noradrenaline concentrations, was similar under both phentolamine and prazosin. There was no direct evidence for the clinical relevance of the more pronounced presynaptic &agr;‐blockade with phentolamine as compared with the almost pure postsynaptic &agr;‐blocking properties of prazosin. Development of tolerance seemed to occur with both drugs; however, haemodynamic benefit in terms of increased stroke volume could only be achieved after chronic treatment.

Kardiovaskuläre Effekte von Dobutamin

SummaryThe cardiovascular effects of dobutamine, a derivative of dopamine have been investigated in seven patients with chronic left ventricular dysfunction. The patients were either suffering from coronary heart disease or from cardiomyopathy.Dobutamine was administered at doses of 2.5–5.0–7.5–10.0 and 15.0 µg/kg/min. The following parameters were measured: aortic pressure, left ventricular pressure (LVEDP, LVdp/dtmax) by using a Millar tip manometer, pulmonary artery pressure and cardiac output (dy-dilution technique).The positive chronotropic effect of dobutamine was small in the lower dosage range and reached significance only with the highest dose of 15.0 µg/kg/min. Systolic aortic pressure was increased moderately over the whole dosage range (p<0.05). However the increment of mean aortic pressure (+11 mm Hg), of stroke volume (+22%) and of stroke work (+49%) was already maximum (p<0.05) at a dose of 5.0 µg/kg/min.The positive inotropic action of dobutamine caused a dose related increase of cardiac index and of LVdp/dtmax of +53% and of +193% respectively. This effect was accompanied by a continuous and significant decrease of LVEDP and of peripheral resistance. Dobutamine induced arrhythmias have not been observed. 15 min after infusion stop, no dobutamine effect could be detected. These findings demonstrate that the actions of dobutamine are not merely cardioselective. However, in the dose range between 2.5 and 15.0 µg/kg/min a positive inotropic effect is predominant. Further clinical trials with dobutamine on patients with severe myocardial dysfunction and low output syndrome may yield promising results.ZusammenfassungDie kardiovaskulären Effekte von Dobutamin, einem Derivat des Dopamin, wurden an 7 Patienten mit chronischer Funktionsstörung der linken Kammer bei koronarer und myokardialer Herzerkrankung untersucht.Dobutamin wurde in steigenden Dosen von 2,5–5,0–7,5–10,0 und 15,0 µg/kg/min infundiert. Gemessen wurden der Druck in der zentralen Aorta, im linken Ventrikel (Kathetertipmanometer; LVEDP, LVdp/dtmax) und in der Pulmonalarterie sowie das Herzminutenvolumen (Farbstoffverdünnungsmethode).Der positiv chronotrope Effekt von Dobutamin war gering und erst bei 15,0 µg/kg/min statistisch auffällig. Der systolische Aortendruck nahm im gesamten Dosisbereich mäßig stark zu. Dagegen war die Zunahme des mittleren Aortendruckes mit 11 mm Hg, die des Schlagvolumens mit 22% und der Schlagarbeit mit 49% bei 5,0 µg/kg/min am größten (p<0,05).Die positiv inotrope Wirkung von Dobutamin führte dosisabhängig zu einer Zunahme des Herzindex und von LVdp/dtmax um maximal 63 bzw. 193% (p<0,01). Dabei sanken der LVEDP und der periphere Widerstand signifikant ab. Arrhythmien traten unter Dobutamin nicht auf. Nach 15 min war die Wirkung der Substanz abgeklungen.Die Befunde zeigen, daß Dobutamin keine streng kardioselektive Wirkung besitzt. Jedoch überwiegt im Dosisbereich von 2,5–15,0 µg/kg/min die positiv inotrope Wirkung. Weitere klinische Untersuchungen mit dieser Substanz an Patienten mit schwerer Herzinsuffizienz und low output Syndrom erscheinen erfolgversprechend.