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S H Hohnloser

Publications and source records attributed to S H Hohnloser.

141 records · Page 8Linked to original sources
PubMed1990

Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase.

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.

Drug Synergism↗
PubMed1989

Comparison of twice daily with thrice daily administered encainide for benign or potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy of encainide administered 2 (group A) or 3 times daily (group B) was evaluated in a randomized, placebo-controlled trial involving 101 patients with benign or potentially malignant ventricular arrhythmias. In group A, encainide was titrated at dosages of 35, 50 and 75 mg twice daily and in group B at dosages of 25, 35 and 50 mg 3 times daily. Drug efficacy, as judged by repeated ambulatory monitoring, was defined as greater than 75% reduction in ventricular premature complexes combined with a greater than 90% abolition of pairs and runs of nonsustained ventricular tachycardia. In group A, 27 of 52 patients (52%) had their arrhythmia suppressed by the drug compared with 34 of 49 (69%) in group B (difference not significant). There was a trend toward better arrhythmia control in group B if a total daily dose of greater than 100 mg was necessary for arrhythmia suppression. Side effects were frequent in both groups (24 vs 28%, difference not significant). Thus, encainide administered twice daily effectively suppresses ventricular arrhythmias in this patient population.

Adult↗
PubMed1989

Electrophysiologic effects of enoximone in patients with congestive heart failure.

The electrophysiologic effects of enoximone were evaluated in 12 patients with idiopathic dilated cardiomyopathy undergoing routine programmed electrical stimulation (PES). Enoximone (1.5 mg/kg for 20 min followed by 0.75 mg/kg for 20 min) significantly shortened the spontaneous sinus cycle length as well as the atrial and ventricular refractory period. Neither during control PES nor during enoximone infusion were sustained ventricular arrhythmias provoked. However, in 5 of 12 patients, there was an increase in the number of repetitive ventricular responses induced by PES during enoximone administration. The observed electrophysiologic changes may be indicators for increased electrical instability of the myocardium in selected patients.

Adult↗
PubMed1988

Intravenous lorcainide for symptomatic ventricular tachyarrhythmias: comparison with lidocaine and oral lorcainide.

Intravenous lorcainide and lidocaine were administered to 25 patients with symptomatic ventricular tachyarrhythmias in a randomized single-blind crossover study. Prior to drug therapy, each patient underwent 48 hours of ambulatory monitoring and exercise testing on a motorized treadmill. At the completion of baseline studies, patients were randomized to receive either lidocaine or lorcainide intravenously. The dose of lidocaine was 1.0 mg/kg by bolus followed by an infusion of 2 to 3 mg/min. The dose of lorcainide was 2.0 mg/kg followed by a constant infusion of 200 to 300 mg over 24 hours. Two patients developed side effects on lidocaine and the infusion was discontinued prior to evaluation of efficacy. Of the remaining 23 patients, 11 (48%) had their arrhythmia controlled, defined as a greater than 90% reduction in repetitive forms (couplets and ventricular tachycardia) and a 50% reduction in ventricular premature beats. Lorcainide was effective in 8 of the 25 patients (32%). There was no correlation between the effect of lidocaine and the response to lorcainide (p = NS). Oral lorcainide therapy was administered to 17 patients who were free of side effects during the intravenous infusion. The oral drug was effective in nine patients (53%), five of whom had responded to the intravenous drug, and was ineffective in eight, seven of whom were also unresponsive to intravenous lorcainide. The intravenous drug predicted the response to the oral form in 71% of patients, but this was not statistically significant. Side effects occurred in 10 patients (59%) and were primarily neurologic.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Spontaneous variability and circadian distribution of ectopic activity in patients with malignant ventricular arrhythmia.

Day to day variability of ventricular ectopic activity was analyzed in 45 patients with a history of malignant ventricular tachyarrhythmias who underwent two successive 24 h periods of ambulatory electrocardiographic (ECG) monitoring in the absence of antiarrhythmic drugs; 26 were male and 19 female, with a mean age of 56 years (range 15 to 76). The total number of single ventricular premature beats, couplets and ventricular tachycardia beats and runs on days 1 and 2 demonstrated a consistent overall correlation (r = 0.76 to 0.84). Individual variability was evaluated by regression analysis with determination of 95% confidence limits. The minimal decrease in arrhythmia density necessary to distinguish true drug effect from spontaneous variability was 64% for single ventricular premature beats, 83% for couplets, 90% for ventricular tachycardia runs and 93% for ventricular tachycardia beats. To meet the criteria for arrhythmia aggravation, the arrhythmia density had to increase by 400, 877, 1,500 and 2,400%, respectively. Multivariate analysis disclosed an inverse relation between day to day arrhythmia variability and baseline arrhythmia density and age. Variability was more pronounced in patients with coronary artery disease but was not influenced by the type of presenting arrhythmia or left ventricular function. The diurnal distribution of arrhythmias and heart rate followed a distinct circadian pattern. These data indicate that, despite good group reproducibility, spontaneous arrhythmia variability in individuals is substantial, necessitating standards to define both drug effect and arrhythmia aggravation.

Adolescent↗
PubMed1987

Predictors of antiarrhythmic drug efficacy in patients with malignant ventricular tachyarrhythmias.

The relationship between arrhythmia density observed during ambulatory monitoring, left ventricular ejection fraction (EF), and response to antiarrhythmic drug therapy was evaluated in 94 patients presenting with ventricular fibrillation (VF) (n = 20) or ventricular tachycardia (VT) (n = 74). Following baseline studies, an average of 4.9 antiarrhythmic drugs were tested singly in each patient. Univariate and multivariate analyses revealed that the density of VT on baseline ambulatory monitoring and initial left ventricular EF were independent predictors of drug efficacy. The 45 patients with an EF less than or equal to 35% responded to 34 +/- 29% of drugs tested, whereas the 49 with an EF greater than 35% had arrhythmia suppression with 46 +/- 28% of agents (p less than 0.038). Patients exhibiting VT during greater than or equal to 50% of monitoring hours responded to 32 +/- 26% of drugs, whereas those with VT during less than 50% of hours showed arrhythmia suppression with 48 +/- 29% of antiarrhythmic agents tested (p = 0.009). During a mean follow-up period of 12.9 months, the annual sudden death mortality for all patients was 9.3%. However, 8 of the 55 patients responding to less than 50% of drugs tested died suddenly and 17 had recurrent VT. By contrast, only 1 of the 39 patients responding to greater than or equal to 50% of the antiarrhythmic drugs tested died suddenly and two experienced recurrent VT (p = 0.00005).(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗
PubMed1987

Influence of beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties and serum potassium concentration in the anesthetized dog.

The influence of selective beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties was studied in 18 anesthetized dogs. Selective beta 2-adrenoceptor activation by salbutamol failed to alter myocardia excitability but significantly lowered serum potassium concentration. Excitability, refractoriness, and ventricular fibrillation threshold were also not changed after administration of 100 and 200 micrograms/kg of the selective beta 2-antagonist ICI 118,551. However, at a dose of 500 micrograms/kg, refractoriness was prolonged and ventricular fibrillation threshold increased. These changes appear to be due to blockade of beta 1-adrenoceptors rather than to membrane stabilizing effects, since in catecholamine-depleted animals even the highest dose of ICI 118,551 did not alter myocardial electrical properties. It is concluded that beta 2-adrenoceptors do not influence electrophysiologic properties of the canine myocardium.

Adrenergic beta-Agonists↗
PubMed1986

Effect of hypokalemia on susceptibility to ventricular fibrillation in the normal and ischemic canine heart.

To examine the impact of hypokalemia on cardiac electrical stability, the thresholds for repetitive extrasystole and ventricular fibrillation were determined before and after potassium depletion in 15 chloralose-anesthetized dogs. A reduction in serum potassium concentration from 3.6 to 2.1 mEq/L induced by hemodialysis decreased the repetitive extrasystole threshold by 30% and the ventricular fibrillation threshold by 25% (p less than 0.01). The increase in ventricular vulnerability following acute coronary occlusion was markedly augmented by concomitant potassium depletion. Thus, hypokalemia enhances the propensity for ventricular fibrillation in the normal as well as in the ischemic canine heart. These findings shed light on clinical observations of enhanced susceptibility to life-threatening arrhythmias during acute myocardial ischemia in hypokalemic patients.

Animals↗
PubMed1986

Effects of adrenergic and muscarinic receptor stimulation on serum potassium concentrations and myocardial electrical stability.

The influence of adrenergic and muscarinic receptor activation on cardiac electrical stability and on serum potassium concentrations was studied in 23 anaesthetised dogs. The ventricular fibrillation threshold was assessed using the single stimulus technique. Adrenaline (1.0 microgram X kg-1 X min-1) caused a brief rise and a subsequent prolonged fall in serum potassium concentration, which was accompanied by a decline in ventricular fibrillation threshold when baroreceptor activation was prevented. After pretreatment with the beta1 adrenoceptor blocking agent metoprolol (0.5 mg X kg-1), adrenaline did not alter vulnerability to ventricular fibrillation but still elicited hypokalaemia. In contrast, selective beta2 adrenoceptor blockade (ICI 118551, 100 micrograms X kg-1) prevented the adrenaline induced lowering of serum potassium concentration but not of ventricular vulnerability. Muscarinic receptor activation by methacholine (3.0 micrograms X kg-1 X min-1) had no effect on serum potassium concentration but increased the ventricular fibrillation threshold by 30%. When methacholine was administered concomitantly with adrenaline the decline in serum potassium concentration persisted, but the increase in ventricular vulnerability was completely prevented. It is concluded that in the normal canine myocardium adrenaline produces an increase in vulnerability that is mediated through beta 1 adrenoceptors and that the beta 2 adrenoceptor mediated hypokalaemia is dissociated from electrophysiological effects of adrenaline. Parasympathetic nervous system activation does not influence serum potassium concentrations but opposes the effects of adrenaline on susceptibility to ventricular fibrillation.

Adrenergic beta-Antagonists↗
PubMed1986

Short- and long-term therapy with tocainide for malignant ventricular tachyarrhythmias.

Tocainide was administered to 228 patients referred for treatment of recurrent ventricular tachyarrhythmias that were refractory to therapy with conventional antiarrhythmic drugs. After baseline studies, 1200 to 2400 mg tocainide/day was given for 4 days. Tocainide was effective in 49% of 180 patients evaluated with monitoring and exercise testing and in 35% of 48 patients undergoing electrophysiologic testing. No clinical parameter predicted the response to tocainide, although there was a correlation with the effect of lidocaine. Tocainide was selected for long-term treatment in 73 patients who were followed for an average of 26.4 months (range 1 to 92 months). The incidence of sudden death was 4.3% per year and two patients had nonfatal recurrence of arrhythmia. It is concluded that tocainide is effective and well tolerated during long-term use if therapy is evaluated carefully and is individualized.

Adolescent↗
PubMedDate not supplied

Effect of coronary ischemia on QT dispersion.

Over the last 5 to 8 years, numerous clinical studies have been conducted evaluating the effects of coronary ischemia on disparity of ventricular repolarization (VR) as assessed by determination of QT dispersion from the surface electrocardiogram. From findings in patients with acute myocardial infarction, stable coronary disease, and vasospastic angina there is convincing evidence that acute coronary ischemia augments inhomogeneity in VR. In some studies, this was associated with the occurrence of ventricular arrhythmias. In general, therefore, these clinical observations confirm previous experimental work. One should keep in mind, however, various problems inherent to the current technology used to determine QT dispersion from the surface electrocardiogram. Whereas some of these technological limitations can be overcome in carefully designed and conducted clinical studies, these methodological shortcomings have so far precluded the routine use of QT dispersion in taking care of patients with acute coronary syndromes. It remains to be seen whether further refinements in technology will enable clinicians to incorporate assessment of disparity of VR in daily practice in an attempt to further improve care of patients with acute coronary syndromes.

Angina, Unstable↗