[Is measuring by portable heart rate monitors (sport watches) dependable in patients with an implanted pacemaker?]. / Messen tragbare Herzfrequenz-Messgeräte (Sportuhren) bei Schrittmacherpatienten zuverlässig?

BACKGROUND AND OBJECTIVE: Regular physical exercise is advantageous for physical fitness and endurance. The intensity of exercising can be controlled by portable heart rate monitors. The aim of the study was to investigate if wearable monitors work properly in pacemaker patients. PATIENTS AND METHODS: In 30 patients with an implanted single or dual chamber pacemaker made by five different manufacturers their heart rate was determined simultaneously by surface ECG and Holter ECG, and was compared with the heart rates derived from portable heart rate monitors (Polar A1) at rest, during 6 minutes in-house walk, and while exercising at 25, 50, and 75 watts in a bicycle exercise test. The tests were done with pacing set at uni- as well as bipolar stimulation mode. RESULTS: At rest in two of 30 patients (6,6 %) paced in unipolar mode the portable heart rate monitors counted double. Under exercise conditions the portable monitors counted double in six of 26 patients (23 %) while being stimulated in unipolar mode. In bipolar stimulation mode, the portable heart rate monitors were working properly in all patients under all conditions. CONCLUSIONS: Patients with an implanted bipolar pacing system can control their physical exercising safely and accurately by means of portable heart rate monitors. Pacemaker patients who are planning regular physical exercising should be provided with an implanted bipolar pacemaker system.

[Thin-walled apical ventricular aneurysm associated with hypertrophic obstructive cardiomyopathy]. / Dünnwandiges Herzspitzenaneurysma bei hypertropher obstruktiver Kardiomyopathie.

HISTORY AND ADMISSION FINDINGS: A 73-year-old patient presented for routine follow-up examination for pre-diagnosed hypertrophic obstructive cardiomyopathy (HOCM). The patient's history included arterial hypertension and dyspnea on exertion. INTERVENTIONS: Echocardiography revealed a large apical aneurysm, which had vastly increased in size over the past six months. Further evaluation by cardiac magnetic resonance (NMR) imaging confirmed the aneurysm and demonstrated a wall thickness of no more than 2 mm. TREATMENT AND COURSE: Due to the rapid increase in size in addition to the extremely thin wall diameter the risk of spontaneous rupture was considered high and the patient was referred to surgical therapy. Echocardiographic and NMR-findings were confirmed intraoperatively. The aneurysm was resected and the postoperative progress was uneventful. CONCLUSION: Aneurysms of the apical left ventricle can result from an underlying HOCM. In case of rapid increase of the aneurysm, aneurysmectomy should be performed.

[Transcatheter closure of atrial septal defects in adults. Practicality and safety of four different closure systems used in 102 patients]. / Katheterinterventioneller Verschluss von Vorhofseptumdefekten im Erwachsenenalter. Durchführbarkeit und Sicherheit bei 102 Patienten unter Verwendung vier verschiedener Verschlusssysteme.

BACKGROUND AND OBJECTIVE: Surgical closure of secundum atrial septal defect (ASD) or patent foramen ovale (PFO) is a procedure with few complications. But this surgical intervention can nowadays be avoided by transcatheter insertion of occluding devices. Such interventional methods must be judged against the results of surgical procedures. This report from one center presents the practicability and safety of different transcatheter occluder systems. PATIENTS AND METHODS: Transcatheter occlusion was undertaken in 102 patients (40 females, 62 males, aged between 17 and 76 years [median age 45]) with either an ASD (41pts.) or a PFO (60 pts.) or with both, in one patient. Four different systems were used: ASDOS (for ASD and PFO), PFO-STAR (for PFO), Amplatzer Septal Occluder (for ASD) or Amplatzer PFO Occluder (for PFO). Follow-up, including transoesophageal echocardiography took place 48 hours, 4 weeks, 6 months and 1 year after the interventional occluder placement. RESULTS: An occluder was successfully placed in the ASD or PFO in 99 of the 102 patients. In three patients the occluder ( ASDOS ASD) could not be correctly ancchored in the defect. In two other patients the same device was subsequently removed surgically because of mispositioning or a large resiudal shunt. Occluder-associated problems were: mild (41%) or extensive (11%) thrombus formation on the occluder without early embolization, residual shunt at one year (ASD 16%, PFO 29%); minor displacement (10%) or broken umbrella strut (6%) of no clinical relevance. One patient required emergency surgical intervention on the day of the transcatheter placement (PFO-STAR) because of pricardial tamponade. Primary complete occlusion was achieved in 71%. There was no case of cerebral emboli. CONCLUSION: Transcatheter occlusion of ASD and/or PFO is a reliable and safe procedure. Regarding peri- and/or postinterventional complications, primary results and practicability, the Amplatzer septal occluder and Amplatzer PFO occluder are particularly advantageous.

[Preventing fat embolism syndrome (FES) in implantation of cemented hip endoprosthesis shafts with a trans-prosthetic drainage system (TDS)]. / Vermeidung des Fettembolie-Syndroms (FES) bei der Implantation von zementfixierten Hüftendoprothesenschäften mit dem Transprothetischen Drainage-System (TDS).

In vitro studies with the transprosthetic drainage system (TDS) have revealed a reduction in intrafemoral pressure in cemented total hip prosthesis. The aim of the present study was to establish whether the incidence of fat embolic syndrome (FES) is also reduced. Ten patients underwent standardized cemented total hip replacement using TDS under standardized general anaesthesia. The usual peri-operative monitoring measures were extended to include cardiopulmonary monitoring (pulmonary artery catheter, intra-arterial blood pressure) and two-dimensional transoesophageal echocardiography. Previous studies had reported an increased risk for fat embolic syndrome with conventional, and even with vacuum cementing techniques. Our recorded cardiopulmonary data and the data provided by two-dimensional transoesophageal echocardiography show a significant reduction in pulmonary embolism with TDS. This technique can be recommended in particular for high-risk patients (osteoporosis, elderly patients) and the implantation of long femoral stems. On the basis of the clinical data, a new femoral stem allowing the use of the TDS technique is being developed.

Transcatheter closure of atrial-septal defects and patent foramen ovale in adults: optimal anatomic adaptation of occlusion device.

BACKGROUND: For transcatheter closure of atrial-septal defects, different occlusion systems are available. The purpose of this study was to examine the clinical feasibility of the ASD Occlusion System (ASDOS, Dr Osypka GmbH, Grenzach-Wyhlen, Germany) and to evaluate the short- and long-term results. METHODS AND RESULTS: The study was composed of 20 consecutive patients with atrial-septal secundum defect (n = 13) or patent foramen ovale (n = 7). The device implantation was successful in all patients. For optimal closure of the defect, left atrial and right atrial umbrellas of different sizes were required in 10 of 20 patients. No major short- or long-term complications occurred. During the mean follow-up period of 13.9 +/- 5 months, 5 strut fractures without dislocation were observed, and in 8 (40%) of 20 patients transesophageal echocardiography revealed a small residual shunt. CONCLUSION: The ASDOS double umbrella system is suitable for transcatheter closure of interatrial defects in selected patients. This system showed a high procedural safety and has the unique advantage of individual adaptation of the occluding device on the defect anatomy that results in high closure effectiveness.

Thrombus formation after transcatheter closure of atrial septal defect.

Thrombotic layers and/or atrial thrombi were detected by transesophageal echocardiography as a usual finding after transcatheter closure of atrial septal defects with the ASDOS device. The size of the thrombotic structures regularly decreased within 6 months without any clinical signs of embolization.

Investigation of the negative inotropic effects of 17 beta-oestradiol in human isolated myocardial tissues.

1. The aim of the present study was to evaluate the effects of 17 beta-oestradiol in human myocardium. The effects of 17 beta-oestradiol, progesterone and testosterone on force of contraction were investigated in electrically driven isolated atrial trabeculae and ventricular papillary muscles from human hearts in the presence and absence of Bay K 8644, a calcium channel agonist. In addition, the effects of 17 beta-oestradiol, progesterone and testosterone on binding of [3H]-PN 200 110 were assessed in membranes prepared from human ventricular myocardium. 2. 17 beta-Oestradiol elicited a negative inotropic effect in atrial (IC50: 7.1 mumol 1(-1), confidence interval 3.8 to 13.4, n = 3) and ventricular preparations (IC50: 4.6 mumol 1(-1)), confidence interval 2.2 to 9.4, n = 3) as compared with solvent controls. There was no significant difference (P > 0.05) of IC50 values in the absence and presence of isoprenaline (0.0 mumol 1(-1)) in atrial (IC50: 10.8 mumol 1(-1), confidence interval 9.1 to 12.9, n = 6) and ventricular preparations (IC50: 9.4 mumol 1(-1), confidence interval 7.3 to 11.9, n = 8). 3. 17 beta-Oestradiol at 30 mumol 1(-1) induced a significant rightward shift of the concentration-response curves for the positive inotropic effect of Bay K 8644 in atrial preparations (EC50: 0.13 mumol 1(-1), confidence interval 0.08 to 0.19, n = 6; EC50 with 17 beta-oestradiol: 0.58 mumol 1(-1), confidence interval 0.33 to 0.83, n = 6, P < 0.05) and ventricular preparations (EC50: 0.07 mumol 1(-1), confidence interval 0.04 to 0.11, n = 8; EC50 with 17 beta-oestradiol: 0.3 mumol 1(-1), confidence interval 0.18 to 0.49, n = 8, P < 0.05). Testosterone, progesterone at 30 mumol 1(-1) and the solvent control had no significant effect on the concentration-response curves to Bay K 8644. 4. In membranes prepared from human ventricular myocardium the effect of 17 beta-oestradiol on binding of [3H]-PN 200 110, an antagonist at the 1,4 dihydropyridine binding site, was not different from that observed with progesterone, testosterone or solvent controls. 5. In myocardial membranes no specific oestrogen receptors were demonstrated by [3H]-oestradiol binding studies. 6. Thus, the calcium antagonistic property of 17 beta-oestradiol cannot be attributed to a direct interaction with 1, 4 dihydropyridine binding sites.

Effects of angiotensin II and angiotensin-converting enzyme inhibitors on human myocardium.

Human myocardial angiotensin II receptors and the angiotensin AT1 and AT2 receptor subtypes were characterised using the partial angiotensin II receptor agonist [125I][Sar1,IIe8]angiotensin II and the selective antagonists losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'((1H-tetrazol-5-yl)biphen yl-4-yl)- methyl]imidazole) and PD 123177 (1-[(4-amino-3-methylphenyl)methyl]-5-(diphenyl-acetyl)- 4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxylic acid). The density of angiotensin II receptors was higher in atrial than in ventricular myocardium. Angiotensin AT2 receptors were predominant in atria and ventricles (80-85% of total angiotensin II receptors). Only in isolated, electrically driven atrial trabeculae but not in ventricular preparations, angiotensin II did produce a concentration-dependent positive inotropic effect, which was antagonized exclusively by the angiotensin AT1 receptor antagonist losartan and which amounted to about 20% of the positive inotropic effect of milrinone and isoprenaline. The application of the angiotensin-converting enzyme inhibitors captopril, enalaprilat and ramiprilat had no inotropic effect in either tissue. It is concluded that angiotensin AT1 receptors exclusively mediate direct positive inotropic effects in atrial myocardium. Since angiotensin-converting enzyme inhibitors do not produce any inotropic effect, tonic regulation of basal force of contraction by angiotensin II does not occur.

Evidence against a role of nitric oxide in the indirect negative inotropic-effect of M-cholinoceptor stimulation in human ventricular myocardium.

Nitric oxide (NO) has been reported to mediate several effects in response to muscarinic cholinergic stimulation in cardiovascular tissues. Recently, an attenuation of guinea pig cardiac myocyte contraction by NO has been described. The aim of the present study was to determine whether the indirect negative inotropic effect of M-cholinoceptor stimulation in human myocardium is in part due to an effect of endogenous NO. Therefore, the effect of carbachol was studied under control conditions and during inhibition of NO-synthase by pretreatment with NG-monomethyl-L-arginine (NMMA). Functional experiments were performed in isolated, electrically driven (1 Hz, 37 degrees C) left ventricular papillary muscle strips of human myocardium. Since cytokines have been reported to be increased in the serum of patients with heart failure and could induce NO-synthase activity in failing myocardium, we compared samples from nonfailing and terminally failing (classified as NYHA IV) hearts. The indirect negative inotropic effect of carbachol (10 mumol/l) was studied in the presence of the beta-adrenoceptor agonist isoprenaline (0.03 mumol/l). After stimulation with isoprenaline, carbachol significantly (P < 0.05) reduced force of contraction. This effect was diminished in failing myocardium compared to nonfailing, probably due to the diminished inotropic response most likely due to the lower cAMP levels in response to beta-adrenoceptor stimulation in the former condition. Pretreatment with NMMA (100 mumol/l) altered the antiadrenergic effect of carbachol neither in nonfailing nor in failing preparations. Furthermore, inhibition of guanylyl cyclase, the target enzyme of NO, by preincubation with methylene blue (10 mumol/l) for 30 min had no effect on the carbachol-induced decrease in force of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for reduction of norepinephrine uptake sites in the failing human heart.

OBJECTIVES: This study investigated the role of neuronal uptake of norepinephrine (uptake-1) in human heart failure as a local factor for altering concentrations of norepinephrine at the cardiac myocyte membranes. BACKGROUND: Several beta-adrenergic neuroeffector defects occur in heart failure. Whether an alteration in norepinephrine uptake-1 occurs is still unresolved. METHODS: The role of norepinephrine uptake-1 was studied in electrically stimulated (1 Hz, 37 degrees C) human ventricular cardiac preparations and isolated myocardial membranes. RESULTS: The effectiveness of norepinephrine in increasing the force of contraction was decreased in relation to the degree of heart failure. In contrast, the potency of norepinephrine was increased in failing hearts (New York Heart Association functional class IV) in relation to the concentrations producing 50% of the maximal effect (EC50). The EC50 values for isoproterenol, which is not a substrate for norepinephrine uptake-1, were reduced in myocardium in functional classes II to III and IV compared with those in nonfailing myocardium. The uptake inhibitors cocaine and desipramine (3 mumol/liter) potentiated the positive inotropic effects of norepinephrine in nonfailing myocardium (p < 0.05) but not in functional class IV myocardium. Radioligand binding experiments using the uptake inhibitor hydrogen-3 mazindol revealed a significant decrease by approximately 30% in norepinephrine uptake-1 carrier density in functional classes II to III and IV myocardium versus nonfailing myocardium (p < 0.05). CONCLUSIONS: In human heart failure, there is a presynaptic defect in the sympathetic nervous system, leading to reduced uptake-1 activity. This defect in the failing heart can be mimicked by the effects of uptake blocking agents, such as cocaine and desipramine, in the nonfailing heart only. Compromised norepinephrine uptake-1 in functional class IV cannot be further increased by cocaine and desipramine. The pathophysiologic consequences could be an increased synaptic concentration of norepinephrine predisposing to adenylyl cyclase desensitization.

Increase of the extracellular magnesium concentration reduces cardiac glycoside toxicity in the human myocardium.

We studied the influence of magnesium on contractility and on force-frequency-relationship as well as on the positive inotropic and toxic effects of ouabain (OUA) on electrically driven human right auricular trabeculae. Radioligand binding experiments were performed with myocardial tissue from nonfailing and from terminally failing patients. Magnesium produced a concentration-dependent negative inotropic effect (P < .05). In contrast, OUA (0.03-0.1 mumol/l) concentration-dependently increased isometric force of contraction. The maximal positive inotropic effect of OUA (5.9 +/- 0.9 mN; 1 mmol/l of magnesium) was unchanged after increasing magnesium from 1 to 2 mmol/l (5.8 +/- 0.9 mN). OUA was as effective as Ca++ (15 mmol/l; 6.7 +/- 0.5 mN). OUA (0.05 and 0.03 mumol/l) exerted toxic effects after 2 hr and 0.08 or 0.1 mumol/l of OUA after 30 min, respectively. Time until toxic effects occurred after OUA (0.1 mumol/l) was significantly longer with 2 mmol/l of magnesium compared to 1 mmol/l of magnesium. In right auricular trabeculae, the force of contraction increased with increasing frequency (0.5-1 .5 Hz) of stimulation. The force-frequency-relationship becomes negative after elevation of extracellular Ca++ (2.4 mmol/l of Ca++) (2 Hz: 92 +/- 5.5% basal). Magnesium restored the force-frequency-relationship in the presence of enhanced Ca++ concentration (2.4 mmol/l of Ca++; 2 mmol/l of Mg++; 2 Hz: 145 +/- 16.9% basal). The receptor-density and affinity measured by [3H]OUA binding was not different in nonfailing and failing myocardium. Magnesium increased concentration-dependently the affinity of [3H]OUA to its receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Existence of PAF receptors in human platelets and human lung tissue but not in the human myocardium.

The aim of this study was to investigate whether platelet-activating factor (PAF), PAF receptors, and PAF receptor-mediated effects in the human myocardium play a role in cardiac depression during anaphylaxis or septic shock. The effects of PAF, the biologically inactive derivative lyso-PAF, and the specific PAF antagonist WEB 2086 were studied in human myocardial tissue, in human coronary arteries, in human platelets, and in human lung tissue. PAF (C16-PAF, C18-PAF; 0.000001 to 1 mumol/L) had no effect on isometric force of contraction of electrically driven right atrial trabeculae (patients undergoing aortocoronary bypass surgery) and left ventricular papillary muscle strips (mitral valve replacement). PAF (0.2 mumol/L) did not influence the concentration-response curve of either the beta-adrenoceptor agonist isoprenaline (ISO, 0.0001 to 1 mumol/L) or the m-cholinoceptor agonist carbachol (CARB, 0.0001 to 10 mumol/L). The effectiveness (ISO +4.7 +/- 0.7 mN, PAF + ISO + 4.3 +/- 0.44 mN, CARB -2.7 +/- 1.06 mN; PAF + CARB -2.6 +/- 0.52 mN) and the potency--as indicated by the EC50 values--of both isoprenaline and carbachol were identical with and without pretreatment with PAF (0.2 mumol/L). PAF at concentrations of 0.000001 to 10 mumol/L exerted no effect on force of contraction either precontracted (prostaglandin F2 alpha, 0.3 mumol/L) or unprecontracted in human coronary artery rings. Histamine (0.01 to 100 mumol/L) and noradrenaline (0.001 to 30 mumol/L) initiated concentration-dependent contraction in human coronary artery rings (EC50: histamine, 1.86 mumol/L; noradrenaline, 0.69 mumol/L). At lower concentrations (PAF, 0.01 mumol/L) PAF produced complete aggregation of human platelets. In human platelet membranes and lung membranes, 3H-WEB 2086 exhibited saturable high-affinity binding (KD 14.4 nmol/L and 14.3 nmol/L). The maximal binding capacity was 292 fmol/mg protein and 268 fmol/mg protein, respectively. In displacement experiments PAF (0.01 to 10000 nmol/L) and WEB 2086 (0.01 to 10000 nmol/L), but not lyso-PAF, completely displaced 3H-WEB 2086 from its binding sites on human and lung membranes. In contrast, neither in left ventricular membranes nor in right atrial membranes was specific binding of 3H-WEB 2086 observed. These results suggest that there are neither specific PAF receptors nor direct PAF-mediated actions in human myocardial tissue or human coronary artery rings. The effects of PAF on myocardial function may be due to the activation of mediators (e.g., histamine).

Effect of the phosphodiesterase inhibitor UK 61260 on human myocardial inotropy and diastolic relaxation.

The phosphodiesterase inhibitor UK 61260 exhibits positive inotropic activity in animal studies and is under clinical investigation for treatment of congestive heart failure (CHF). We examined the lusitropic and inotropic responses to UK 61260 in electrically driven (1 Hz, 37 degrees C) human auricular trabeculae (AUT, aortocoronary bypass operation, nonfailing hearts, n = 13) and in papillary muscle strips (PAP) from moderately (New York Heart Association, NYHA II-III, mitral valve replacement, n = 6) and terminally (NYHA IV, heart transplantation, n = 7) failing human hearts. For comparison, we studied the effects of UK 61260 after prestimulation with forskolin (FOR 0.03 microM) and isoprenaline (ISO 0.03 microM), as well as the effects of milrinone (MIL 1-1,000 microM), ISO (0.01-10 microM), ouabain (OUA, 0.1 microM), and Ca2+ (1.8-15 mM) in failing human myocardium alone. UK 61260 increased force of contraction (FOC), peak rate of tension increase (+T) and decay (-T) significantly (p less than 0.01) in AUT but not in PAP of NYHA II-III and NYHA IV. Only after prestimulation (FOR and ISO), was UK 61260 effective in stimulating FOC in NYHA II-III and NYHA IV. UK 61260 increased (p less than 0.01) +T and -T, resulting in a shortening of twitch time. As judged from the EC50 values, UK 61260 increased FOC more potently than MIL. The effectiveness of OUA and Ca2+ in increasing developed tension in human failing myocardium was significantly higher as compared with UK 61260. We conclude that during stimulation of the cardiac beta-adrenoceptor-adenylate-cyclase system, UK 61260 increases myocardial systolic and diastolic function in failing human myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Force-frequency relationship and inotropic stimulation in the nonfailing and failing human myocardium: implications for the medical treatment of heart failure.

In isolated papillary muscle strips from nonfailing donor hearts (NF) and from the hearts of patients with dilated cardiomyopathy with severe heart failure (NYHA IV), the force-frequency relationship was studied. Experiments were performed under basal conditions and in the presence of 0.01 microM or 0.1 microM isoprenaline and 0.02 microM ouabain. In NF, there was a positive inotropic effect following an increase of the stimulating frequency, whereas in NYHA IV, the force gradually declined under these conditions. Low concentrations (0.01 microM) of isoprenaline prevented the negative inotropic effect in NYHA IV, whereas at 0.1 microM the mechanical function deteriorated in NF and NYHA IV. Ouabain had no effect on the force-frequency relationship compared to basal conditions. It is concluded that a reduction of high frequencies does improve the contractility in the failing myocardium. It is not unreasonable to speculate that this mechanism might be involved in the beneficial effects of drugs which reduce the heart rate, such as beta-adrenoceptor antagonists and cardiac glycosides, in the condition of congestive heart failure in which the sympathetic tone is high.