Pregnancy in heart and heart-lung transplant recipients.
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Abortion, Induced↗
Biomedical subjects
H Aass
Publications and source records attributed to H Aass.
Bipolar radiofrequency catheter ablation creates confluent lesions at larger interelectrode spacing than does unipolar ablation from two electrodes in the porcine heart.
AIMS: Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart. METHODS AND RESULTS: In vitro, confluent lesions were reliably created by a 'dielectrode' catheter (energy delivered simultaneously (in parallel) from two 4 mm electrodes spaced 1 mm apart, towards an indifferent electrode), and a 'bipolar' catheter (energy delivered (in series) between two 4 mm electrodes spaced 5 mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30 s duration (70 degrees C) were administered to the inferior vena cava-tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4 h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length x width x depth measured 7.4 (2.4) x 5.4 (2.2) x 2.8 (0.8) mm in the standard unipolar mode, 10.2 (1.4) x 6.3 (0.7) x 3.3 (1.1) mm in the dielectrode mode and 14.0 (3.6) x 6.0 (1.7) x 3.8 (1.2) mm in the bipolar mode. Thus lesion length increased significantly through the three groups (P < 0.001), while width and depth did not. CONCLUSION: Both dielectrode and bipolar ablation were feasible in porcine right atrial ablation, and created longer lesions than the standard unipolar mode. By allowing a larger interelectrode distance, bipolar ablation created the longest lesions and may be favourable when linear lesions are necessary.
Animals↗
Radiofrequency current ablation of porcine right atrium: increased lesion size with bipolar two catheter technique compared to unipolar application in vitro and in vivo.
Interruption of atrial flutter and fibrillation by RF catheter ablation may be favored by large, elongated lesions. We administered RF current in unipolar and bipolar mode in porcine right atrium. Bipolar ablation was performed between the tip electrodes of two serially coupled catheters. With 4-mm tip electrodes in vitro, lesion length increased from a mean (SD) of 7.9 (1.2) mm at 3 mm-interelectrode distance (i.e.d.) to 13.3 (3.3) mm at 9-mm IED, but decreased at 12-mm IED due to nonconfluent lesions (P < 0.0001). With 4 mm distal electrodes and 8 mm IED, bipolar lesions were 65% longer than corresponding unipolar ablations. Switching to bipolar mode increased the lesion length more than increasing electrode tip length to 6 mm in unipolar mode. Power and temperature controlled ablation created equally sized lesions. Twelve anesthetized pigs were randomized to unipolar or two catheter bipolar temperature controlled ablation of the right atrial free wall. Bipolar ablation created confluent lesions with endocardial length x width of 13.5 (5.8) x 7.3 (3.7) mm, unipolar ablation 6.4 (2.8) x 4.6 (1.4) mm (P < 0.001 when comparing length and P = 0.013 for lesion width). The atrial lesions in both groups were transmural and extended into hilar lung lesions with maximal depth of 3.0 (1.1) and 2.6 (1.0) mm, respectively (P = 0.44). Five bipolarly and four unipolarly ablated pigs developed right diaphragmal paresis. We conclude that bipolar ablation may be preferable in situations where large, elongated lesions are favorable. The two catheter technique is feasible in porcine right atrium. Both bipolar and unipolar ablation of the porcine right atrial free wall may frequently be complicated by injury to the phrenic nerve and adjacent lung tissue.
Animals↗
[Serum digitoxin in concomitant use of antiepileptics in routine therapy].
Concomitant use of digitoxin and enzyme-inducing antiepileptics may lower serum levels, and accordingly the effect of digitoxin, unless the higher metabolic clearance is compensated for by higher dosage. Use of digitoxin is almost always guided by serum concentration measurements. Information on a possible enzyme-inducing effect of phenobarbital, phenytoin and carbamazepine is easily accessible. Compilation of serum level measurements for digitoxin showed that serum levels shifted towards lower values during concomitant use of phenytoin or carbamazepine than when digitoxin was used alone. As a consequence, the fraction of patients with serum levels below the therapeutic range was doubled. Concomitant use of phenobarbital did not cause a shift in the levels of digitoxin. In fact, in this group, a larger fraction of the serum level measurements were within the therapeutic range. Thus, the dosage of digitoxin appears to be fully compensated during concomitant use of phenobarbital, but obviously deserves attention during concomitant use of phenytoin or carbamazepine.
Anticonvulsants↗
[Heart rate variability. Parameters for risk stratification after myocardial infarction].
Reduced heart rate variability (HRV) is an independent risk factor after myocardial infarction, indicating higher risk of fatal and nonfatal arrhythmias and of cardiac death in general. Analysis of HRV is also a valuable tool in clinical research, providing a non-invasive measurement of fluctuations in sympathetic and parasympathetic activation. We expect increased use of these methods, since new 24-hour: ECG-monitoring equipment is to be delivered with software for HRV as an option. Statistical time domain analysis of the whole 24-hour system of recording is very suitable for stratifying risk after myocardial infarction. Frequency domain analysis requires manual as well as automatic editing, but is the method of choice in clinical research involving short-term recordings and standardized conditions.
Autonomic Nervous System↗
Temperature guided radiofrequency catheter ablation of myocardium: comparison of catheter tip and tissue temperatures in vitro.
Temperature monitoring during RF ablation has been proposed as a means of controlling the creation of the lesion. However, in vivo studies have shown poor correlation between lesion size and catheter tip temperature. Thus, we hypothesized a difference between catheter tip and tissue temperatures during RF catheter ablation, and that this difference may depend on flow passing the ablation site, tip electrode length, and catheter-tissue orientation. In vitro studies were performed using four different ablation catheters (tip electrode length: 2, 4, or 6 mm) with a thermistor or a thermocouple as temperature sensor. Set temperature was 70 degrees C and pulse duration was 30 seconds. Pieces of porcine left ventricle were immersed in a bath of isotonic saline-dextrose solution at 37 degrees C. The ablation catheters were positioned perpendicularly, obliquely, or parallel to the endocardium. A temperature sensor was inserted from the epicardial side and positioned 1 mm beneath the catheter-tissue interface. Experiments were made with a flow of 200 mL/min passing the ablation site or with no flow. The catheter tip and tissue temperatures differed significantly (P < 0.0001) during ablation. This difference increased with time, with flow passing the ablation site, with the length of the tip electrode, and when the catheter was positioned perpendicularly or obliquely to the endocardium as compared to the parallel catheter-tissue orientation (P < 0.05). In conclusion, the tissue temperature may far exceed the catheter tip temperature, and intramyocardial superheating resulting in steam formation and popping may occur despite a relatively low catheter tip temperature.
Animals↗
Comparison between alpha-1 adrenoceptor-mediated and beta adrenoceptor-mediated inotropic components elicited by norepinephrine in failing human ventricular muscle.
The purpose of our study was to investigate the inotropic response to the endogenous agonist norepinephrine mediated through alpha-1 adrenoceptors and to compare this response to that mediated through beta-adrenoceptors in failing human ventricular myocardium. We studied ex vivo the inotropic effect of norepinephrine in isometrically contracting trabecular myocardium from both ventricles of explanted hearts. By studying influence of appropriate adrenoceptor blockers, qualitative characteristics of the inotropic response and sensitivity of the inotropic response to cholinergic stimulation, it was revealed that norepinephrine evoked both alpha-1 and beta adrenoceptor-mediated inotropic effects in failing human ventricle myocardium. Quantitatively the inotropic responses to norepinephrine varied markedly between preparations, but the mean responses elicited through the respective adrenoceptor systems were of comparable magnitude. Concomitant stimulation of alpha-1 and beta adrenoceptors by norepinephrine alone revealed a contribution of an alpha-1 adrenoceptor-mediated component to the final and unopposed inotropic response. Differential sensitivity of the two adrenoceptor systems to norepinephrine depending on etiology of heart failure and possibly also thyroid status was observed. It is concluded that norepinephrine evokes an alpha-1 adrenoceptor-mediated inotropic effect comparable to that evoked through the beta adrenoceptors in failing human ventricular myocardium, and that this alpha-1 adrenoceptor-mediated inotropic effect may be of functional importance.
Adrenergic Antagonists↗
[Ablation of the bundle of His in atrial arrhythmia. A solution when the drugs fail].
Radiofrequency ablation of the bundle of His was performed in 33 patients with intractable atrial arrhythmias (fibrillation in 23, flutter in seven, atrial tachycardia in three). Complete AV block was produced in 30 patients, and clinically satisfactory incomplete block in another two. All were subsequently treated by pacemaker. The ablation was a failure in one patient with hypertrophic cardiomyopathy. Today ablation can be targeted at atrial tachycardias and flutter, and ablative modification of the AV node can reduce ventricular rate in chronic atrial fibrillation. However, His bundle ablation is still the treatment of choice in drug refractory atrial fibrillation when no other measure can provide adequate rate control.
Adult↗
[Radiofrequency ablation of heart arrhythmias. Results in the first 150 patients treated at the Arrhythmia center in Oslo].
The authors review the first 150 patients with cardiac arrhythmias who were treated with radio-frequency ablation at a Norwegian arrhythmia centre. The clinical success rate (either electrophysiological cure or a dramatic reduction in the severity and frequency of the attacks) was 97%. 11 patients were treated for two or more arrhythmias. In 27 patients two, occasionally three, sessions were required to obtain a satisfactory clinical result. Repeat ablation is scheduled for three cases where the treatment was unsuccessful. Among 190 ablations, 13 complications occurred, none of which resulted in permanent sequelae. The time spent on each procedure, and particularly the long time spent on fluoroscopy during the earlier procedures, demonstrates the existence of a learning curve for ablation. This lends support to the authorities' restriction of treatment of arrhythmias by ablation to only two laboratories in a population of four million.
Adolescent↗
Effects of combined radiofrequency and direct current energy catheter ablation on ventricular myocardium in pigs.
When radiofrequency catheter ablation of ventricular arrhythmias is unsuccessful, an option may be to combine it with direct current energy. We therefore investigated the effects of such a combination. Radiofrequency energy was delivered in a bipolar or unipolar fashion to the left and right ventricles through an ablation catheter with a tip electrode 2 mm long, using a temperature-guided radiofrequency generator. Radiofrequency ablation was followed by a single cathodal direct current shock (66 J) with the ablation catheter positioned similarly in six closed-chest pigs. In a control group (six animals) only direct current ablation was performed, with one or two energy applications (66 J) in each ventricle. Two of six animals in the radiofrequency/direct current group died due to perforation in the follow-up period, 1 and 3.5 h after the direct current ablation, respectively. Gross pathological examination of the hearts revealed transmural lesions in all animals. In the radiofrequency/direct current group four lesions were perforated, three of which were located in the left ventricle. There was a significant increase in the number of perforations in the radiofrequency/direct current group compared to the control group, where perforation was never observed. Haemorrhagic pericardial fluid was found in five of the six animals in the radiofrequency/direct current group compared to none in the control group. These findings show that myocardial ablation with radiofrequency energy followed by direct current energy in the same session may have a high complication rate.
Animals↗
Power and temperature guided radiofrequency catheter ablation of the right atrium in pigs.
The aim of the present study was twofold: to assess the safety of ablating the atrial free wall using RF current; and to assess the effect of a single dose of intravenous heparin followed by aspirin once daily to prevent thrombus formation after RF ablation. Temperature and power guided catheter ablation were evaluated. Twenty pigs were randomized to power or temperature guided unipolar RF catheter ablation. Ten animals received a bolus of heparin (150 U/kg) followed by 150-mg aspirin daily, and ten served as controls. A mid-sternal thoracotomy was performed 5-7 days later. The ability of a lesion to resist an increased transmural atrial pressure was examined by inflating a cuff around the pulmonal artery. Transmural lesions were found in all animals. Right atrial pressure was increased from 5 to 30 mmHg with no sign of perforation. In 11 of 20 (55%) animals, 1-3 lesions were found in the lungs (diameter 4-18 mm). The localization of these lesions corresponded to the lesions in the atria. There were no differences in the energy delivery modes with regard to the number of animals with lung lesions. Lesions with thrombus formation were found in four animals in the heparin/aspirin group and in nine animals in the control group. The incidence of thrombi was significantly smaller in the treatment group. There were no differences between temperature and power guided catheter ablation with regard to the size of the atrial lesions or to the incidence of thrombus formation. Transmural lesions induced in the right atrium by RF energy are resistant to increases in transmural pressure. However, lung tissue overlying the ablated target may be injured by the RF energy delivered. The combination of a single dose intravenous heparin followed by aspirin daily may reduce the incidence of thrombus formation.
Animals↗
[Therapeutic drug monitoring with the help of serum concentration measurements. How are the analytic results distributed in a population?].
Therapeutic drug monitoring includes measurement of serum concentrations of drugs when this is possible and appropriate. A therapeutic range is defined for populations where the serum levels represent an optimal relationship between clinical effects and side effects for most of the individuals in the population. Compared with the rest of the population, some individuals are atypical, both with respect to response to and elimination of drugs. Therapeutic drug monitoring makes individualization of dosages in these individuals easier, but often requires extra effort. Compilation of serum level measurements for different drugs for a period of six months showed that the tailoring of digitoxin, carbamazepine, lithium and phenobarbital is as close to optimal as can be expected for a population. For amitriptyline, digoxin and theophylline, a considerable increase in clinical effect within a population of users could probably be achieved by bringing more individual serum levels from the subtherapeutic into the therapeutic range. Nor does the therapeutic potential of phenytoin, nortriptyline and valproate seem to be fully utilized.
Blood Chemical Analysis↗
Acute haemodynamic effects of isradipine in hypertensive heart transplant recipients.
The acute haemodynamic effects of the new calcium antagonist isradipine have been studied in ten hypertensive cardiac transplant recipients. Isradipine 0.01 mg.kg-1 was given IV during right heart catheterization and noninvasively automatic blood pressure measurements. From a baseline blood pressure of 164/114 mmHg the maximum blood pressure reduction was 35 mmHg systolic, 30 mmHg diastolic, and mean 34 mmHg, due to a reduction in systemic vascular resistance, maximum 43%. Cardiac index increased 32%, mainly due to an increase in the stroke volume, as the heart rate rose only by 10%. Left ventricular filling pressure was slightly reduced. We conclude that the main effect of isradipine was a major reduction in left ventricular afterload, comparable to that previously found in other patient groups.
Heart Transplantation↗
The effect of temperature-guided radiofrequency ablation of ventricular myocardium.
The safety and feasibility of temperature-guided radiofrequency (RF) ablation of ventricular myocardium were assessed in an open-chest animal model. RF ablation was performed in the ventricles of 19 pigs using ablation catheters with a tip electrode of 2 or 4 mm length. The energy was delivered in a bipolar (2 mm tip electrode only) or unipolar configuration. Set temperature ranged from 60 to 90 degrees C. Pulse duration was 30 s. Histological examination showed coagulation necrosis with a haemorrhagic zone. However, lesions with a deep cleavage were found after five unipolar (2 mm tip electrode) energy applications. No such lesions were found after unipolar energy applications with a 4 mm tip electrode. During or shortly after ablation, premature ventricular beats and non-sustained VT were frequently observed and in some instances ventricular fibrillation. In the bipolar mode we found a positive correlation between lesion area/volume and peak temperature with a correlation coefficient of 0.48 and 0.56, respectively (P < 0.05). However no correlation was found between lesion size and applied energy. In the unipolar configuration there was no correlation between lesion size and these parameters. Median depth and area were: bipolar: 4.0 mm/23.5 mm2, unipolar (2 mm tip electrode): 3.5 mm/12.2 mm2, unipolar (4 mm tip electrode): 4.0 mm/15.7 mm2. We conclude that in a beating heart it is difficult to predict lesion size from temperature or energy.
Animals↗
Both alpha 1- and beta-adrenoceptor stimulation determine the time course of the inotropic effect of noradrenaline in rabbit heart.
It has been a matter of controversy whether alpha 1-adrenoceptor stimulation contributes to the final inotropic and lusitropic responses in mammalian myocardium to noradrenaline during concomitant and unopposed beta-adrenoceptor stimulation. In the present paper we report studies that compare time courses of the inotropic and lusitropic responses to separate and combined alpha 1- and beta-adrenoceptor stimulation, respectively, in electrically driven rabbit papillary muscles by a submaximal concentration of noradrenaline. Separate alpha 1- or beta-adrenoceptor stimulation (presence of appropriate receptor blocker) showed the characteristic slow and fast development, respectively, of the inotropic responses. Qualitatively, the respective characteristic changes were also observed: alpha 1-adrenoceptor stimulation caused a negative lusitropic effect giving a prolongation of the time to peak tension (TPT), while beta-adrenoceptor stimulation caused a pronounced positive lusitropic effect giving a shortening of TPT. The time course of the inotropic response to combined adrenoceptor stimulation had characteristics that deviated from the respective time courses to separate alpha 1- or beta-adrenoceptor stimulation thus indicating a contribution from both adrenoceptor populations to the final inotropic response. Combined alpha 1- and beta-adrenoceptor stimulation gave a pronounced positive lusitropic response as might be expected due to the obviously dominating role of the beta-adrenergic component. However, the maximal lusitropic effect and the shortening of TPT were both slightly less during combined adrenoceptor stimulation compared to separate beta-stimulation thus indicating an influence of the alpha 1-adrenoceptor mediated negative lusitropic effect. Quantitatively, the separate alpha 1- and the separate beta-adrenoceptor mediated inotropic effects were not additive. In accordance with other recent studies, this indicated an inhibitory interaction between the two adrenergic receptor populations in myocardium.
Animals↗
Prazosin-sensitive component of the inotropic response to norepinephrine in rabbit heart.
Earlier experiments have usually failed to demonstrate a competitively displaceable alpha adrenoceptor blocker-sensitive component in the dose-dependent inotropic response to norepinephrine in mammalian hearts. We reinvestigated if it was possible to reveal this phenomenon by carefully choosing a concentration of the alpha adrenoceptor blocker prazosin that would give a significant displacement while it still was possible to completely surmount the blockade by reasonable concentrations of norepinephrine. Both inotropic and lusitropic dose-dependent responses to norepinephrine in rabbit heart papillary muscles were recorded. In the presence of 3 X 10(-9) M prazosin there was a significant rightward shift of a component corresponding to about 20% of the total inotropic response to norepinephrine. The prazosin-sensitive component was shifted significantly more to the left by 3 X 10(-5) M cocaine than the nonsensitive component. The maximal inotropic response to norepinephrine was increased at lower prazosin-concentrations (3 X 10(-9) M), whereas at 10(-7) M prazosin the maximal response was unchanged compared to the absence of prazosin. The maximal lusitropic response to norepinephrine was increased monophasically and dose-dependently by prazosin. Thus, by carefully considering the relative potencies of the agonist and the antagonist it was possible to demonstrate an alpha adrenoceptor blocker sensitive component in the inotropic response to norepinephrine in rabbit heart. The effect of cocaine upon the prazosin-sensitive component would indicate that the alpha adrenoceptor population in rabbit myocardium is located more closely to the sympathetic nerve endings than the beta adrenoceptor population.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Adrenoceptors in myocardial regulation: concomitant contribution from both alpha- and beta-adrenoceptor stimulation to the inotropic response.
The studies presented deal with the alpha 1-adrenoceptor mediated inotropic effects of noradrenaline obtained by exclusive ("pure") alpha 1-adrenoceptor stimulation or by concomitant stimulation of alpha 1- and beta-adrenoceptors in myocardium. The pure beta-adrenergic effects of noradrenaline were also quantified. Interactions between the two receptor systems were studied. The pure alpha 1- and beta-adrenergic effects of noradrenaline, respectively, were achieved separately in the presence of high concentrations of appropriate receptor blockers. The experiments were performed on isolated ventricular myocardium from rat, rabbit, and man. The pure alpha 1-adrenergic inotropic effects were about 35-50% of control (basal) and half the pure beta-adrenergic effects both in rat and rabbit myocardium. Ventricular myocardium from man exhibited an alpha 1-adrenergic inotropic effect of the same magnitude (50% of control [basal]) as did rabbit papillary muscle. Determination of the alpha 1-adrenergic inotropic component during concomitant beta-adrenoceptor stimulation was associated with difficulties. Several experimental approaches on rat and rabbit myocardium are presented and discussed. Some types of experimental approaches obviously underestimate the alpha 1-adrenergic component. The methods regarded as reliable revealed an alpha 1-adrenergic inotropic effect of about 20-30% during combined adrenoceptor stimulation by noradrenaline. Concomitant beta-stimulation reduced the alpha 1-adrenergic effect by about 50%, while alpha 1-stimulation attenuated the beta-effect to a lesser degree (about 20-25%). A model is presented on a mutual attenuation of the functional expression of the two receptor systems.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Increase of cyclic AMP in subcellular fractions of rat heart muscle after beta-adrenergic stimulation: prenalterol and isoprenaline caused different distribution of bound cyclic AMP.
Although prenalterol is a partial beta-agonist, it has been reported to produce only a marginal, non-significant increase of cAMP in rat hearts. We studied the effect of prenalterol and isoprenaline on free and bound cAMP content in subcellular fractions of perfused rat hearts to see whether prenalterol increased cAMP and whether there were differences in the subcellular distribution of the cAMP contents after stimulation with the drugs. The in situ binding characteristics of cAMP to the protein kinases at different degree of beta-adrenergic stimulation were elucidated. Prenalterol increased significantly both total cAMP content in homogenate, bound cAMP in a 100,000 g particulate fraction and bound, free and total cAMP contents in the resulting supernatant. While prenalterol increased bound cAMP in the particulate fraction and in the supernatant proportionally, isoprenaline caused a relatively greater increase of bound cAMP in the supernatant. At equieffective concentrations regarding inotropic and lusitropic effects, prenalterol and isoprenaline increased bound cAMP in the particulate fraction to the same degree, while the increase in the other fractions was greater after isoprenaline. Thus, the cAMP bound in the particulate fraction seemed to determine the inotropic state of the cell after beta-adrenergic stimulation, supporting a compartmentation of cAMP in myocardium. In controls 31 to 34% of the total binding capacity for cAMP in the particulate fraction was occupied, increasing to 77% after maximal beta-stimulation. The binding capacity in the supernatant was only 15 to 18% saturated in the basal situation and about half saturated after maximal beta-stimulation. cAMP bound in the particulate fraction is of special interest when cAMP and functional effects are studied.
Animals↗