[Induction and increase of cardiac arrhythmia by anti-arrhythmia agents].
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Anti-Arrhythmia Agents↗
Biomedical subjects
H Just
Publications and source records attributed to H Just.
[Therapy of heart failure with vasodilator agents].
Vasodilation in congestive heart failure is an established therapeutic principal. The ventricular unloading improves contractile geometry and thereby improves working conditions for the contractile element: myocardial oxygen consumption falls and myocardial efficiency improves. This effect is independent from the vasodilating substance employed; it is, however, dependent on the simultaneous induction of pre- and afterload reduction. Vasodilation improves regional perfusion. Differential improvement in organ bloodflow is related to the type of vasodilator employed. It seems essential for a therapeutic benefit that renal and coronary perfusion are improved and that shunt flow, especially with steal phenomena, is avoided. Skeletal muscle bloodflow improves only slowly under ACE-inhibitor therapy. It could be shown that the immediate vasodilation due to ACE inhibition is followed by a second phase of vasodilation, which may be related to the influence of ACE inhibition of intraarterial wall angiotensin converting enzyme. Another factor possibly responsible for the delayed response to vasodilation in congestive heart failure, may be functional and structural changes in skeletal muscle. Reversal of these changes requires time. Both factors - the vessel wall related mechanism, as well as changes in parenchymal structure and function - require prolonged periods of treatment until therapeutic benefit can be seen.
Angiotensin-Converting Enzyme Inhibitors↗
Coronary thrombolysis in man with pro-urokinase: improved efficacy with low dose urokinase.
Single-chain urokinase-type plasminogen activator (scu-PA), was given to 20 patients with acute myocardial infarction first alone (group I; n = 9) and then in combination with an initial bolus injection of 200,000 units of urokinase (group II; n = 11). In group I, scu-PA was administered in a dose of 15 mg up to 60 mg as an infusion over one hour. Complete reperfusion was achieved in 3/9 patients after 50 to 60 min and partial reperfusion in an additional 2 patients. In group II, a bolus injection of urokinase and 48 mg of scu-PA over one hour were given. Reperfusion was achieved in 9/11 patients after a mean of 30 +/- 22 min. Fibrinogen, alpha 2-anti-plasmin and plasminogen levels did not change from baseline in group I. In group II, fibrinogen levels decreased slightly from 272 +/- 84 mg% to 178 +/- 82 mg% (p less than 0.05) after two hours. No bleeding complications were encountered. Reocclusion at 24 hours was evaluated in 18 patients and was not seen. It was concluded that an initial bolus of urokinase improves the efficacy and the rate of thrombolysis by scu-PA.
Adult↗
[Therapeutic systems--possibilities and limits].
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Administration, Cutaneous↗
Therapeutic advances in heart failure.
Annual mortality from congestive heart failure ranges from 15% to 60%, depending on the severity of the left ventricular damage and underlying disease. Most controlled trials have been too small to detect any beneficial effect on survival from the newer vasodilator and inotropic drugs. However, the results of two recent studies strongly suggest that some vasodilator drugs improve prognosis. In one study, a hydralazine-nitrate combination reduced 2-year mortality by 34%, while in another study, enalapril, in addition to diuretics, digitalis, and directly acting vasodilators, reduced 1-year mortality by 31%. Thus far no large studies have been published with the new phosphodiesterase-inhibiting agents. Although preliminary reports of large-scale trials did not demonstrate changes in survival rate, they have been shown to improve well-being in class III-IV congestive heart failure patients.
Heart Failure↗
[Acute myocardial infarct. A changing clinical picture].
Acute myocardial infarction is a major complication of stenosing coronary artery disease and constitutes the most frequent single cause of death. It is caused by thrombotic occlusion of one of the major epicardial coronary arterial branches in most cases. Sudden death due to ventricular fibrillation is responsible for the majority of early fatalities. In 60% of all fatal infarcts, death occurs within 1 h of the onset of pain. The final extension of myocardial necrosis is reached within 2-4 h. An integrated programme has therefore been developed for the surveillance and treatment of patients suffering acute coronary attack; it has been shown that it can markedly lower infarct mortality. It includes mobile prehospital care, intensive care treatment in the hospital, and rehabilitative procedures for application during reconvalescence. Early antiarrhythmic treatment and myocardial reperfusion via fibrinolysis are the main therapeutic procedures in the earliest stage. In hospital an operating room and an operating team must be available round the clock for the performance of coronary angiography followed by percutaneous transluminal coronary angioplasty or bypass surgery, which can be safely carried out in the acute stage providing the indications are strictly observed. Mortality and morbidity can be significantly lowered and both life expectancy and quality of life can be remarkably improved.
Humans↗
[Bepridil--electrophysiologic properties of a new calcium antagonist with an anti-arrhythmia effect].
In 12 patients with recurrent pre-syncope or syncope and suspected sick sinus syndrome, the electrophysiologic properties of bepridil were tested using 1-2 extrastimuli during four basic pacing rates. Bepridil was given in a dose of 5 mg/kg body weight over 10 min. It caused no significant changes in sinus cycle length (+5%) and corrected sinus node recovery time during pacing of 100/min (-6%), 120/min (+8%) and 140/min (+4%). The conduction times PQ- (+10%) and QRS-interval (+6%) increased significantly, AH- (+8%) and HV-interval (+5%) were slightly prolonged. Antegrade Wenckebach point increased from 460 to 508 ms (p less than 0.05). The effective refractory period was prolonged in the atrium (+11%, p less than 0.05), the AV-node (+14%, p less than 0.05) and the right ventricle (6-11% at pacing rates 100-140/min, p less than 0.05 for each cycle length). In relation to the pacing rate, QTc-interval increased highly significantly (p less than 0.01) by 16% (sinus rhythm), 12% (100/min), 20% (120/min) and 19% (140/min). After a mean of 5 min after the start of infusion a doubled T-wave was observed in 11/12 patients, persisting during Holter monitoring for several hours without evidence of increased incidence of spontaneous ventricular arrhythmias. During programmed electrical stimulation with 1-2 extrastimuli, no increase in vulnerability of the right ventricle was obvious in any patient.
Adolescent↗
[Progress in clinical cardiology. 1. Coronary angiography].
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Cardiology↗
Evaluation of long-term oral levodopa therapy in chronic congestive heart failure.
To evaluate the long-term effects of orally administered levodopa, 11 patients with chronic congestive heart failure (NYHA III-IV) were studied during maintenance therapy (30 +/- 1 days) and after withdrawal from levodopa. The daily levodopa dose was 4 g in six patients; because of side effects the levodopa dose was reduced to 2-3 g in the remaining patients. After withdrawal of levodopa, mean pulmonary capillary wedge pressure and mean right atrial pressure increased significantly (from 19 +/- 2 to 24 +/- 3 and from 7 +/- 2 to 9 +/- 2 mmHg, respectively). Effective renal plasma flow was 329 +/- 57 during levodopa therapy and decreased significantly to 252 +/- 27 ml/min after withdrawal of levodopa. The number of ventricular premature contractions and couplets increased during levodopa therapy and decreased again significantly after withdrawal of levodopa. No significant differences between on and off levodopa were observed in resting heart rate, arterial blood pressure, cardiac index, stroke work index, systemic vascular resistance, sodium and water excretion, or creatinine clearance. Seven patients improved on levodopa therapy by one NYHA class; four of these seven patients deteriorated again by one NYHA class after withdrawal of levodopa. Regarding both clinical and hemodynamic changes after withdrawal of levodopa, three patients were classified as responders to long-term levodopa therapy. All three responders received 4 g levodopa per day. Average dopamine plasma level was 5.3 +/- 0.8 ng/ml in the responder group and 2.0 +/- 0.5 ng/ml in the nonresponder group. Long-term administration of oral levodopa is associated with beneficial clinical and hemodynamic response in only a minority of patients with chronic congestive heart failure.
Administration, Oral↗
[Hemodynamic effect of intravenous diltiazem and nifedipine in acute myocardial infarct. A randomized study].
In a prospective, randomized trial of 28 patients with acute myocardial infarction nifedipine or diltiazem were administered intravenously and hemodynamic parameters and drug plasma levels measured for 24 hours. Both drugs lowered arterial blood pressure and peripheral resistance. Only diltiazem reduced heart rate and the heart rate x arterial pressure product, as pointer to a reduction in myocardial oxygen consumption. On the other hand, nifedipine is more likely to cause a (reflex) increase in heart rate. In no patient was there evidence of drug-induced hemodynamic impairment. Left ventricular filling pressure was reduced in those patients in whom it had been elevated. While a steady-state plasma concentration was quickly reached with nifedipine, in some patients diltiazem infusion produced a continuous rise in plasma concentration and, in two patients with posterior-wall infarction, high-grade a-v block (reversible after discontinuation of the drug). The results indicate that under ECG control both drugs can be used intravenously without much risk. The hemodynamic profile of diltiazem (reduction in peripheral resistance and heart rate) would seem to be particularly favorable in acute infarction, while nifedipine is preferred in acute infarction plus hypertension. The possible effect on a-v conduction is to be watched on intravenous administration of diltiazem, while in normotensive patients nifedipine may cause an undesirable (reflex-mediated) sympathetic activation.
Adult↗
Cardiac energetics after intravenous enoximone in idiopathic dilated cardiomyopathy.
The acute effects of enoximone on left ventricular (LV) function, myocardial oxygen metabolism and central and systemic hemodynamics were investigated in 12 patients with idiopathic dilated cardiomyopathy. Enoximone was administered intravenously at a rate of 12.5 mg/min; the average dose was 1.42 mg/kg. LV systolic pressure decreased significantly (p less than 0.01) from 128 +/- 18 to 96 +/- 16 mm Hg (mean +/- standard deviation), LV end-diastolic pressure from 16 +/- 3 to 5 +/- 3 mm Hg, LV end-diastolic volume from 288 +/- 43 to 210 +/- 58 ml, LV end-diastolic wall stress from 33 +/- 15 to 11 +/- 5 10(3) dynes/cm2 and LV peak systolic wall stress from 243 +/- 73 to 159 +/- 42 10(3) dynes/cm2. Heart rate increased from 86 +/- 18 to 100 +/- 20 beats/min, ejection fraction from 43 +/- 7 to 52 +/- 14% (p less than 0.05). Cardiac index, stroke volume index and dP/dtmax did not change significantly. Systemic vascular resistance decreased significantly (p less than 0.01) from 1,311 +/- 444 to 1,027 +/- 356 dynes s cm-5, mean pulmonary artery pressure from 13 +/- 6 to 8 +/- 2 mm Hg, mean right atrial pressure from 4 +/- 2 to 2.6 +/- 2 mm Hg and mean arterial pressure from 95 +/- 13 to 74 +/- 13 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Determination of aortic valve orifice area in aortic valve stenosis by two-dimensional transesophageal echocardiography.
Two-dimensional transesophageal echocardiography was used to measure aortic valve orifice area in 24 patients with aortic valve stenosis (AS) and 15 patients without aortic valve disease. Using transesophageal echocardiography, orifice area could be measured in 20 of 24 patients with AS. With transthoracic echocardiography, orifice area could be determined in only 2 of 24 patients. In patients with AS, orifice area determined by transesophageal echocardiography was 0.75 +/- 0.34 cm2 and that calculated with Gorlin's formula was 0.75 +/- 0.32 cm2. In normal aortic valves, orifice area was 3.9 +/- 1.2 cm2 by transesophageal echocardiography. A good correlation was demonstrated between aortic valve orifice area determined using transesophageal echocardiography and calculated orifice area using Gorlin's formula in patients with AS: r = 0.92, standard error of estimate = 0.14 cm2. The absolute difference between orifice area measured with both methods ranged from 0.0 to 0.4 cm2 (mean 0.09 +/- 0.1). In 4 patients orifice area could not be determined with transesophageal echocardiography. The orifice could not be identified in 2 patients because an appropriate cross-sectional view of the aortic valve could not be achieved and in 2 patients with pinhole stenosis (aortic valve orifice area 0.3 cm2). These data show that aortic valve orifice area can be measured reliably using 2-dimensional transesophageal echocardiography.
Aged↗
Transesophageal echocardiography for diagnosis of rupture of the ventricular septum or left ventricular papillary muscle during acute myocardial infarction.
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Echocardiography↗
Influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide.
The influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide was investigated in nine patients with congestive heart failure. The diuretic response to piretanide correlated significantly with the pretreatment cardiac index (r = 0.90). Furthermore, a significant correlation was found between the pretreatment fractional sodium excretion and the cardiac index (r = 0.85). The fractional sodium excretion is reciprocal to the renal sodium and water reabsorption. No change in the hemodynamics was observed prior to the onset of diuresis. At 120 minutes after administration of piretanide, the reduction of mean pulmonary capillary wedge pressure (r = 0.88) and mean right atrial pressure (r = 0.80) was significantly related to the diuretic response. We conclude that the reduced diuretic response to piretanide in patients with low cardiac index is due to increased renal sodium and water reabsorption. The hemodynamic changes following the administration of piretanide are dependent on the diuresis.
Adult↗
Hemodynamics and myocardial oxygen metabolism of pulsus alternans in patients with dilative cardiomyopathy.
The hemodynamic and myocardial energetic changes due to pulsus alternans were investigated by left and right heart catheterization and by oxygen consumption measurements in three patients with dilative cardiomyopathy. In all three patients, pulsus alternans developed after intravenous administration of the phosphodiesterase inhibitor enoximone. Following enoximone (Patients 1/2/3), left ventricular peak systolic pressure was reduced, in the respective patients, from 100/103/115 mmHg (normal beat) to 91/96/94 mmHg (strong beat) and further to 59/80/85 mmHg (weak beat); left ventricular end-diastolic pressure was reduced from 24/23/22 mmHg (normal beat) to 5/10/6 mmHg (strong beat) and further to 3/7/4 mmHg (weak beat). Cardiac output increased by an average of 16%. Heart rate increased by an average of 12%. Stroke work (during pulsus alternans mean between strong and weak beats) did not change (less than 5%) in any of the three patients. Arterial-coronary-sinus oxygen content difference decreased by 5%/13%/22, respectively. Myocardial oxygen consumption per beat decreased in Patient 1 by 8%, in Patient 2 by 8% and remained unchanged in Patient 3. It is concluded that pulsus alternans occurred in consequence of alternating systolic performance. The alternation in systolic performance most probably resulted from a disturbance in excitation-contraction coupling induced by enoximone. The pronounced reduction of left ventricular preload following administration of enoximone may have augmented further the differences between the strong and the weak beat. A disturbance in myocardial oxygen metabolism was ruled out as the cause of pulsus alternans in these patients.
Adult↗
Energetic aspects of inotropic interventions in rat myocardium.
Contractile force of the myocardium can be increased by different molecular mechanisms, and therefore different energetic consequences may result. The influence of the inotropic substances isoproterenol and UDCG-115 on myocardial energetics in isometrically contracting left ventricular rat papillary muscles was investigated by means of highly sensitive antimony bismuth thermopiles. Isoproterenol increased total heat and initial heat by 147% (p less than 0.01) and 69% (p less than 0.02) when normalized to tension-time integral, respectively. No significant change of both heat terms occurred due to UDCG-115. Initial heat was separated into tension-independent heat ("calcium cycling") and tension-dependent heat ("cross-bridge cycling") by means of a new method using 2,3-butanedione monoxime. Both tension-dependent heat per tension-time integral and tension-independent heat increased significantly, due to isoproterenol, from 4.9 +/- 1.17 to 7.6 +/- 2.72 mu cal/g.cm.s (p less than 0.05) and from 0.15 +/- 0.06 to 0.22 +/- 0.04 mcal/g (p less than 0.01). UDCG-115 influenced neither tension-independent heat nor tension-dependent heat per tension-time integral significantly. Thus, the economy of force development was not significantly altered due to UDCG-115 whereas isoproterenol significantly increased the energy necessary for activation, i.e. calcium cycling, and the energy necessary for force production, i.e. cross-bridge cycling. The basic mechanisms of these energetic changes are discussed.
Animals↗
Acute and chronic changes of myocardial energetics in the mammalian and human heart.
In earlier studies using papillary muscles of the rat left ventricle and highly sensitive thermopiles we demonstrated that the heat liberated per gram of myocardium per unit of developed tension-time integral is decreased when the rats suffered from hypothyroidism or renal hypertension. This increase in economy of force production was shown to be associated with a decrease in myosin-ATPase activity and a change in isomyosin composition. In a recent study we showed an increase in heat per gram of mammalian myocardium per tension-time integral of 70% after application of isoproterenol. In order to study the relationship between energy costs and developed tension-time integral in the human heart, haemodynamics and myocardial oxygen consumption were measured. The data were obtained using a Millar microtip catheter pressure transducer and the argon method. Haemodynamics and myocardial energetics were analysed in 8 patients without significant heart disease before and after application of isoproterenol and in 10 patients with dilative cardiomyopathy (NYHA II-III). During one cardiac cycle, myocardial oxygen consumption per gram of LV myocardium per beat (MVO2/g x beat) is related to LV stress-time integral (integral of sigma xt). The economy of myocardial contraction (EC) was calculated by (formula; see text) EC was 11.3 +/- 3.2 in normal and 14.3 +/- 4.7 dyn x s x g/cm2 x mu cal in dilative cardiomyopathic hearts (NS). Isoproterenol decreased EC from 11.3 +/- 3.2 to 5.5 +/- 1.6 dyn x s x g/cm2 x mu cal in the normal hearts (p less than 0.01). In the rat myocardium, changes in economy of force generation were found due to catecholamines, pressure overload and hypothyroidism. In the human heart, similar energetic changes were observed due to catecholamines. No significant differences in energy of force production were seen between normal and dilative cardiomyopathic hearts. The effect of catecholamines in the mammalian and human myocardium is explained by changes in activation processes and in chemomechanical energy transduction at the level of the contractile proteins.
Acute Disease↗
Influence of phosphodiesterase inhibition on myocardial energetics in dilative cardiomyopathy.
The effects of inhibition of phosphodiesterase by enoximone on left ventricular haemodynamics and myocardial energetics were investigated in 10 patients with idiopathic dilative cardiomyopathy. After intravenous administration of enoximone, there was a significant reduction of left ventricular systolic pressure from 126 +/- 21 to 93 +/- 16 mm Hg, of left ventricular end-diastolic pressure from 16 +/- 8 to 5 +/- 3 mm Hg and of left ventricular end-diastolic volume from 287 +/- 54 to 215 +/- 69 ml. Left ventricular pressure-volume work decreased significantly from 12.1 +/- 3.6 to 7.6 +/- 2.8 mm Hg.l. Heart rate was 87 +/- 17 before and 103 +/- 18 min-1 after administration of enoximone (p less than 0.01). Left ventricular systolic stress-time integral, a major determinant of myocardial oxygen consumption, decreased by 49% from 91 +/- 32 to 46 +/- 15 10(3) dyn.s/cm2 (p less than 0.01). In contrast myocardial oxygen consumption per beat was reduced by only 18%, from 138 +/- 28 to 113 +/- 17 microliters O2/100 g (p less than 0.01). The economy of myocardial contraction as calculated by the ratio of systolic stress-time integral to myocardial oxygen consumption per beat was 675 +/- 192 before and 370 +/- 128 dyn.s.100 g/cm2.microliter O2 after administration of enoximone. In conclusion, the phosphodiesterase inhibitor enoximone exhibits vascular and myocardial effects. The myocardial effects result in decreased economy of myocardial contraction. The possible molecular mechanisms of these energetic changes are discussed.
Cardiomyopathies↗