PubMed Health⌕ Search

Biomedical subjects

C Linde

Publications and source records attributed to C Linde.

At least 37 records · Page 2Linked to original sources
PubMed1997

Activators of protein kinase A induce a glibenclamide-sensitive 86Rb+ efflux in rat isolated aorta.

The effect of activators of protein kinase A on membrane K+ permeability and the interaction of these compounds with cromakalim, an opener of ATP-sensitive K+ channels (K(ATP) channels), were investigated. Membrane K+ permeability was assessed by measuring 86Rb+ efflux from rings of rat aorta. Forskolin, an activator of adenylate cyclase, and isobutylmethylxanthine (IBMX), a nonselective phosphodiesterase inhibitor, induced small, concentration-dependent increases in tracer efflux up to 20-40% over the basal level. The effect of forskolin was abolished by the K+ channel blocker tedisamil (1 microM) and partially inhibited by glibenclamide (1 microM), a relatively selective blocker of K(ATP) channels. Further studies were conducted in the presence of 35 mM KCI in the bath in order to increase the size of the 86Rb+ efflux stimulated by forskolin and IBMX. At high concentrations, these compounds produced a biphasic effect with a peak increase being followed by a lower plateau value. Glibenclamide inhibited the 86Rb+ efflux response to forskolin and IBMX by 50-80%. The K+ channel blockers tedisamil (1 microM), Ba2+ (1 mM) and tetraethylammonium (10 mM) also reduced the peak response to forskolin by about 50% and abolished or greatly inhibited the plateau response. In addition to the small effect on basal 86Rb+ efflux, forskolin (0.3 microM) increased cromakalim-induced 86Rb+ efflux 3.4 times. At higher concentrations, however, a concentration-dependent inhibition was observed with an IC50 value of 7.6 +/- 0.4 microM. 1,9-dideoxyforskolin, which does not increase cAMP, increased neither basal nor cromakalim-induced 86Rb+ efflux; however, it inhibited cromakalim-stimulated tracer efflux with an IC50 value of 22 +/- 2 microM. It is concluded that forskolin and IBMX, probably by increasing intracellular cAMP levels, induce a 86Rb+ efflux from rat aorta, the major part of which is glibenclamide-sensitive and may pass through K(ATP) channels. In addition, low concentrations of forskolin greatly facilitate the K(ATP) channel opening effect of cromakalim whereas high concentrations block the channel; this blocking effect of forskolin is unrelated to the cAMP elevating action.

Animals↗
PubMed1997

Inhibition by protein kinase C of the 86Rb+ efflux and vasorelaxation induced by P1075, a K(ATP) channel opener, in rat isolated aorta.

In rat aortic rings, P1075, an opener of ATP-dependent potassium channels (K(ATP) channels), produces relaxation and 86Rb+ efflux from preloaded tissues; the increase in 86Rb+ efflux qualitatively reflects K(ATP) channel opening. In this study we have investigated the effects of protein kinase C modulation on the 86Rb+ efflux stimulating, the vasorelaxant and the binding properties of P1075. Phorbol 12,13-dibutyrate (PDBu), a direct activator of protein kinase C, inhibited the 86Rb+ efflux produced by P1075 with an IC50 value of 20+/-2 nM. Phorbol 12-myristate 13-acetate (PMA), another stimulator of protein kinase C, was 150 times weaker in this respect whereas 4alpha-PDBu, the inactive stereoisomer of PDBu, was ineffective. Staurosporine (300 nM), an inhibitor of protein kinase C, induced a small but significant increase of P1075-induced tracer efflux and partially reversed the inhibitory effect of PDBu on P1075-stimulated tracer efflux. The vasorelaxant effect of P1075 was inhibited only to a moderate degree by PDBu at concentrations which inhibited P1075-induced 86Rb+ efflux to >90%; however, in the presence of PDBu, the relaxation kinetics of P1075 were increasingly slowed. The vasorelaxant effect of P1075 in the presence of PDBu was still sensitive to inhibition by glibenclamide (100 nM), the standard inhibitor of the K(ATP) channel openers. Specific binding of [3H]-P1075 to rat aortic rings was unaffected by PDBu and PMA even in the micromolar concentration range. The data show that stimulation of protein kinase C inhibits the K+ channel opening effect of P1075 in rat aorta and suggest that protein kinase C may exert a weak tonic inhibition on the K(ATP) channels in this vessel under quasiphysiological conditions. At concentrations of PDBu which essentially abolished P1075-induced tracer efflux, the glibenclamide-sensitive vasorelaxant effect of P1075 was slowed down but not prevented; this supports earlier suggestions that K+ channel openers are also able to relax smooth muscle cells by a mechanism independent of K(ATP) channel opening.

Adenosine Triphosphate↗
PubMed1997

Interaction between thiol-modifying agents and P1075, a K(ATP) channel opener, in rat isolated aorta.

In vascular smooth muscle, openers of ATP-dependent potassium channels (K(ATP) channels), such as P1075 (N-cyano-N'-(1,1-dimethylpropyl)-N"-3-pyridylguanidine), produce relaxation. In this study we have investigated the effects of thiol-modifying agents on the binding of P1075 and on the 86Rb+ efflux stimulating and vasorelaxant effects of the opener in rat aortic rings. The increase in 86Rb+ efflux induced by P1075 was taken as a qualitative measure of K+ channel opening. The hydrophilic SH-group-oxidizing substance, thimerosal (1 to 100 microM), abolished specific binding of [3H]-P1075 with an IC50 value of 7.6+/-1.2 microM; at 30 microM, the half time for inhibition was 38 min. Two other thioloxidizing agents, PMB (4-hydroxy-mercuribenzoic acid) and DTBNP (2,2'-dithio-bis(5-nitropyridine)), inhibited binding up to 86% and 44%, respectively. The disulphide bond reducing substance, DTT (1,4-dithiothreitol, 0.1 to 1 mM), reduced [3H]-P1075 binding by up to 20% and partially reversed the inhibitory effect of thimerosal. In 86Rb+ efflux experiments, thimerosal (3 to 100 microM) concentration-dependently increased basal efflux but inhibited P1075-stimulated tracer efflux with an IC50 value of 7+/-1 microM. The inhibitory effect occurred with a half-time of approximately 8 min and was essentially reversed by DTT. In rings precontracted with noradrenaline, thimerosal inhibited the vasorelaxant effect in a noncompetitive manner, shifting the concentration-relaxation curves to the right and reducing maximum relaxation. The data show that oxidation of thiol groups interferes with the binding of the K(ATP) channel opener, P1075; concomitantly, the 86Rb+ efflux stimulating and the vasorelaxant effects are inhibited. Reduction of disulphide bonds by DTT has only minor effects on the action of P1075. Collectively, the results suggest that intact thiol groups are essential for the functioning of the K(ATP) channel in rat aorta. The different kinetics governing the inhibition of opener binding and of opener-stimulated 86Rb+ efflux suggest that the SH-groups involved in the two processes differ in their accessibility to thimerosal and/or in their reactivity.

Animals↗
PubMed1997

Long-term effects of dual chamber pacing in patients with hypertrophic cardiomyopathy without outflow tract obstruction at rest.

BACKGROUND: Atrioventricular-synchronous pacing is beneficial in patients with hypertrophic obstructive cardiomyopathy. The effects of pacing in patients without significant left ventricular outflow tract obstruction at rest are, however, less well explored. This study compares the long-term outcome of pacing patients with and without significant left ventricular outflow tract obstruction at rest. METHODS: Forty-one patients with hypertrophic obstructive cardiomyopathy were studied, 19 with a left ventricular outflow tract gradient < 40 mmHg at rest, but exceeding 50 mmHg during provocation with isoproterenol (group A), and 22 with a left ventricular outflow tract obstruction > 40 mmHg at rest (group B). Before the implantation of a permanent pacemaker, the patients were studied according to a temporary pacing protocol. This included graded isoproterenol provocation of the left ventricular outflow tract obstruction, which was assessed by echo Doppler. Following permanent pacemaker implantation, the patients were regularly followed up with echo Doppler, exercise testing and monitoring of the clinical condition. RESULTS: Isoproterenol provocation was reproducible and the technique did not cause any clinically important side effects. Left ventricular outflow tract gradient reduction after chronic pacing did not differ between the two groups. In group A, it decreased from 98 +/- 30 mmHg in sinus rhythm to 42 +/- 26 mmHg during pacing. The corresponding values in group B were 87 +/- 40 mmHg to 36 +/- 24 mmHg. The clinical condition improved similarly in the two groups. Exercise capacity increased significantly and perceived dyspnoea and angina pectoris were significantly lower at submaximal levels of exercise after 6 months of pacing. CONCLUSION: Hypertrophic obstructive cardiomyopathy patients who only exhibit significant left ventricular outflow tract obstruction during provocation benefit as much from pacemaker treatment as do patients who already have significant obstruction at rest. Isoproterenol is a safe and reproducible method for pre-pacing evaluation of hypertrophic obstructive cardiomyopathy patients.

Adult↗
PubMed1997

Pacing in hypertrophic obstructive cardiomyopathy. A randomized crossover study. PIC Study Group.

BACKGROUND: Uncontrolled studies have shown that short atrioventricular delay dual chamber pacing reduces outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Although the exact mechanism of this beneficial effect is unclear, this seems a promising potential new treatment for hypertrophic obstructive cardiomyopathy. METHOD: In order to evaluate the impact of pacing therapy, were performed a randomized multicentre double-blind cross-over (pacemaker activated vs non activated) study to investigate modification of echocardiography, exercise tolerance, angina, dyspnoea and quality of life in 83 patients with a mean age of 53 (range 22-87) years with symptoms refractory or intolerant to classical drug treatment. RESULTS: After 12 weeks of activated or inactivated pacing, independent of which phase was first, the pressure gradient fell from 59 +/- 36 mmHg to 30 +/- 25 mmHg (P < 0.001) with active pacing. Exercise tolerance improved by 21% in those patients who at baseline tolerated less than 10 min of Bruce protocol; symptoms of dyspnoea and angina also improved significantly from NYHA class 2.4 to 1.4 and 1.0 to 0.4, respectively (P < 0.007). Quality of life assessment with a validated questionnaire objectivated the subjective improvement. CONCLUSION: Pacemaker therapy is of clinical and haemodynamic benefit for patients with hypertrophic obstructive cardiomyopathy, left ventricular outflow gradient at rest over 30 mmHg who are symptomatic despite drug treatment.

Adult↗
PubMed1996

Influence of right ventricular pacing site on left ventricular outflow tract obstruction in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was designed to show the influence of right ventricular pacing site on left ventricular outflow tract obstruction during pacing treatment of patients with hypertrophic obstructive cardiomyopathy. BACKGROUND: Atrioventricular synchronous pacing has been reported to reduce left ventricular outflow obstruction and symptoms in patients with hypertrophic obstructive cardiomyopathy. A paradoxic septal movement induced by right ventricular pacing has been implicated as the mechanism behind the reduced left ventricular outflow tract obstruction; however, the importance of pacing site has not been clarified. METHODS: Cardiac output, measured invasively, and left ventricular outflow tract gradient, estimated by Doppler echocardiography, were studied in 15 patients with hypertrophic obstructive cardiomyopathy. Measurements were made with the right ventricular electrode in the septal and apical positions during temporary pacing and during sinus rhythm. RESULTS: Right ventricular apical pacing reduced the outflow tract gradient in all 15 patients to a mean +/- SD of 38 +/- 24 mm Hg from 96 +/- 33 mm Hg during sinus rhythm. During high septal pacing the outflow tract gradient was not reduced, remaining at 93 +/- 44 mm Hg. No significant changes in cardiac output were seen when levels during sinus rhythm (6.4 liters/min), apical pacing (6.4 liters/min) and high septal pacing (5.6 liters/min) were compared. CONCLUSIONS: The right ventricular pacing site is of crucial importance for reducing left ventricular outflow tract obstruction when patients with hypertrophic obstructive cardiomyopathy are treated with pacing. Cardiac output is not reduced by apical pacing.

Adult↗
PubMed1995

Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure.

To verify that atrioventricular (AV) synchronous pacing (DDD) with short AV delay improves the condition of patients with severe congestive heart failure, we implanted DDD pacemakers in 10 patients with severe heart failure (New York Heart Association [NYHA] class III to IV). One day after pacemaker implantation, the AV delay was optimized by Doppler echocardiographic measurements over the aortic outflow tract. Patients were evaluated regarding NYHA class, stroke volume, cardiac output, ejection fraction, and quality of life at 1, 3, and 6 months after pacemaker implantation. Although the optimized AV delay was associated with short-term improvement in stroke volume and cardiac output (baseline stroke volume = 22 +/- 7 ml, day 1 = 28 +/- 12 ml; p = 0.03: baseline cardiac output = 1.9 +/- 0.6 L/min, day 1 = 2.2 +/- 1.1 L/min; p = 0.10), the mean stroke volume, cardiac output, NYHA class, and ejection fraction did not change significantly after 1, 3, and 6 months of pacing compared with baseline values. Three patients improved in NYHA class during the follow-up. A consistent improvement in stroke volume, cardiac output, NYHA class, and ejection fraction was observed in only 1 patient. In conclusion, we found no beneficial effects of AV-synchronous pacing with optimized AV delay in patients with severe heart failure.

Adult↗
PubMed1995

Potentiation of P1075-induced K+ channel opening by stimulation of adenylate cyclase in rat isolated aorta.

1. The effects of analogues and stimulators of cyclic AMP on the 86Rb+ efflux-stimulating and binding properties of P1075, an opener of ATP-dependent potassium channels, were studied in rat aortic rings. The increase in 86Rb+ efflux stimulated by P1075 was taken as a qualitative measure of K+ channel opening. 2. Forskolin, a direct activator of adenylate cyclase, isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, and dibutyryl-cyclic AMP (db-cyclic AMP), a membrane permeant cyclic AMP-analogue, relaxed rat aortic rings contracted by noradrenaline with EC50 values of 0.06, 2 and 10 microM, respectively. 3. Forskolin, IBMX and db-cyclic AMP produced concentration-dependent increases of the 86Rb+ efflux induced by P1075 (50 nM) by up to twofold with EC50 values of about 0.1, 1.7 and 81 microM. At these concentrations the agents had little effect on the basal rate of 86Rb+ efflux. 4. The 86Rb+ efflux produced by P1075 in the presence of the cyclic AMP stimulators was inhibited by glibenclamide, a blocker of ATP-sensitive potassium channels. 5. IBMX (100 microM) induced a leftward shift of the concentration-86Rb+ efflux curve of P1075 without increasing the maximum. The enhancements of P1075-stimulated 86Rb+ efflux produced by combinations of forskolin and IBMX were either additive or less than additive. 6. The protein kinase A inhibitor, H-89, inhibited P1075-stimulated 86Rb+ efflux in the presence of IBMX significantly more than in the absence of IBMX, suggesting that the effect of increased cyclic AMP levels is mediated by protein kinase A. 7. At high concentrations, forskolin and IBMX slightly increased basal 86Rb+ efflux and inhibited the tracer efflux induced by P1075.8. Binding of [3H]-P1075 to rat aortic rings was either unaffected or inhibited by forskolin, IBMX and db-cyclic AMP.9. This study shows that moderate stimulation of the cyclic AMP system potentiates the K+ channel opening effect of P1075 by activation of protein kinase A. The fact that binding of [3H]-P1075 remains unchanged or is diminished favours the hypothesis that the K'channel openers activate ATP-dependent K+ channels by an indirect mechanism.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Outcome of 6-week treatment with transcutaneous electric nerve stimulation compared with splint on symptomatic temporomandibular joint disk displacement without reduction.

The aim of the present study was to compare the effect of transcutaneous electric nerve stimulation (TENS) with the flat occlusal splint in the treatment of temporomandibular joint (TMJ) disk displacement without reduction. Thirty-one patients were included and randomly selected to be treated 6 weeks with either TENS (90 Hz, 30 min, three times/day) or with a flat occlusal splint (24 h/day. Those selected for the TENS group had one electrode placed over the painful TMJ and another electrode over the anterior temporal muscle. The splint group used a conventional flat occlusal splint with cuspid guidance. Both treatment groups visited the clinic once a week. Symptoms and signs were registered before and after treatment. The intensity of pain was recorded with a visual analogue scale (VAS) and with an electronic pocket-sized recorder (Pain-Track) carried 1 week before and also the last week of treatment for continuous registration of pain. Measured with the VAS, half of the patients treated with splints became pain-free or their TMJ pain improved at least 50% both at rest and with jaw function compared with only 6% in the TENS-treated group. With regard to strictly chewing pain, the VAS-registered pain improved in two-thirds of the splint group, compared with 50% of the TENS group. With the Pain-Track device it was found that in most individuals pain was aggrevated at mealtimes. The conclusion was that flat occlusal splints in several respects are better than TENS in the treatment of symptoms associated with TMJ disk displacement without reduction.

Adolescent↗
PubMed1995

Naming notes: transitions from free text to structured entry.

To practice medicine in the near future, health care providers in the USA need an information infrastructure they do not yet have. We offer a contribution from social science research to discussions of current medical records practices and how health care activity systems may be transformed by the advent of electronic health records. The goal of the paper is to set forth a framework that connects over-arching questions concerning medical informatics systems development with the practical, cultural and conceptual issues involved in transitions from handwritten and other free text documentation to structured entry of medical records to build patient profiles. The research is broadly framed by an interest in how reciprocal modifications of the design and use of an electronic health record are negotiated in an iterative prototyping project. It is conducted as part of a complex multi-disciplinary research and development effort to create an electronic health record prototype for use in the integrated health care delivery environment of the Southern California Kaiser Permanente Medical Care Program.

Ambulatory Care↗
PubMed1994

Atrial rate adaptive pacing: what happens to AV conduction?

To investigate if an nonphysiological prolongation of the AV interval is common during activity sensor modulated atrial rate adaptive (AAIR) pacing, 21 patients with sinus node disease treated with fixed rate atrial (AAI) or AAIR pacemakers were examined. Spike-Q intervals were compared at different heart rates obtained by overdrive pacing at rest and during exercise (Study I), measured during exercise at unresponsive (AAI), optimal (AAIR) and over responsive programming (AAIR+) of the activity sensor (Study II), and finally examined by 24-hour Holter recording in AAI and AAIR pacing modes (Study III). Study I: The spike-Q interval increased significantly with increasing heart rate at rest, but not during exercise. At rest the spike-Q interval was significantly higher at all heart rates compared to exercise. There was a significant positive correlation between the maximal spike-Q interval at rest and the maximal spike-Q interval during exercise (r = 0.63). Study II: The spike-Q interval was shortest in the AAI and longest in the AAIR+ mode in all patients. Study III: During AAI or AAIR pacing the spike-Q interval was longest at night and shortest in the morning. The mean spike-Q interval was longer in AAIR than in AAI pacing. No statistical difference between the maximal spike-Q intervals observed during the two modes was, however, found. Variations in spike-Q interval are generally caused by changes in autonomic tone or medication with drugs with antiarrhythmic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1990

Clinical signs in patients with disk displacement versus patients with myogenic craniomandibular disorders.

Patients with disorders of the masticatory system were clinically examined with reference to tender TMJs and sore muscles of the head and neck, jaw movement range, occlusal interferences, and aberrations of the bite. The 158 patients were divided into three groups according to diagnosis: 46 with reducing disk displacement, 57 with nonreducing disk displacement, and 55 with myogenic CMD. Unilateral symptoms were found in 83% of the two TMJ groups and 47% of the myogenic CMD group. At intraoral palpation, significantly more patients with nonreducing disk displacement displayed tender sites on the symptomatic side. Tender TMJ, crepitation, and restricted condylar translation on the symptom side were significantly more common in the group with nonreducing disk displacement. Mean maximal mouth opening was 31 mm in the nonreducing disk displacement, 42 mm in the reducing disk displacement, and 47 mm in the myogenic CMD group. Total laterotrusion was significantly less in the nonreducing disk displacement group. Myogenic CMD patients had more interferences in retruded position on the symptomatic side and more tender neck and shoulder muscles. Patients with nonreducing disk displacement displayed more signs from the masticatory system than those with myogenic CMD.

Adolescent↗
PubMed1989

Subjective symptoms in patients with temporomandibular joint disk displacement versus patients with myogenic craniomandibular disorders.

Signs and symptoms in the masticatory system can be caused by several specified diseases leading to diagnostic problems. This investigation compared patients with temporomandibular joint disk displacement and patients with complaint of myogenic craniomandibular disorders. In association with the onset of the patient's problem, a physical event was found in half the number of patients with permanent disk displacement, compared with only 27% in the myogenic craniomandibular disorders group. Patients with permanent disk displacement reported more pain in the temporomandibular joint ear and jaw region in association with jaw function whereas patients with myogenic craniomandibular disorders reported more bruxism and dental discomfort.

Adolescent↗