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Biomedical subjects

J P Bagger

Publications and source records attributed to J P Bagger.

At least 37 records · Page 2Linked to original sources
PubMed1998

A new method for combined isometric and isobaric pharmacodynamic studies on porcine coronary arteries.

1. The principal aim of the present study was to explore the isometric and isobaric capacity of a new intravascular technique, impedance planimetry, in basic pharmacodynamic investigations on porcine isolated epicardial coronary arteries. 2. The balloon-based catheter technique provides simultaneous measurements of luminal cross-sectional area and pressure. Sources of errors that may influence the accuracy of measurements were evaluated in detail. 3. Under isometric conditions, the stretch ratio-tension diagram showed typical developments of resting and active tensions of the smooth muscle when exposed to alternating maximal K+ depolarization and mechanical stretching. The mean (+/- SEM) maximum active tension was 28.43 +/- 1.72 mN/mm, which was reached at a stretch ratio of 1.26 +/- 0.02, corresponding to a resting tension of 10.50 +/- 0.53 mN/mm (n = 7). The concentration-response relationship to K+ at optimal basal tension was characterized by a mean (+/- SEM) pD2 value of 1.67 +/- 0.01 (n = 7). 4. Under isobaric conditions in the pressure range 40-140 mmHg, the method allowed the investigation of active vascular responses to partial K+ depolarization. The maximal active response to 25 mmol/L K+ was found at the transmural pressure of 60 mmHg (n = 7). To obtain full K+ concentration-response curves, a basal tension corresponding to a transmural pressure of 120 mmHg was required. The mean (+/- SEM) pD2 value for the concentration-response relationship to K+ was 1.53 +/- 0.01 (n = 10). 5. The vascular sensitivities to cumulatively added K+ and various agonists, such as acetylcholine, 5-hydroxytryptamine and noradrenaline, obtained from the same vessel segment at the same initial conditions corresponding to 120 mmHg were significantly higher with the isometric than with the isobaric approach. 6. The results of the present study suggest that impedance planimetry could be a useful tool in pharmacological and physiological investigations of medium-sized arteries, both under isometric and isobaric conditions.

Acetylcholine↗
PubMed1998

Regional differences in the vasorelaxant effects of nicorandil and amlodipine on isolated porcine coronary arteries.

The vasorelaxant effects of nicorandil, a K(+)-channel opener, and amlodipine, a dihydropyridine-type Ca(2+)-channel blocker, were investigated on partially and maximally K(+)-depolarized ring preparations from the porcine left anterior descending coronary artery. By comparing vascular responses in the proximal and distal parts of the epicardial segment, the scope of the study was to evaluate regional differences in the action of nicorandil and amlodipine. Nicorandil (10(-7)-10(-4) M) shifted the K+ concentration-response curves to the right and depressed the maximal contractile responses in a concentration-dependent manner, consistent with K(+)-channel opening and secondary non-K(+)-channel opening mechanisms of action. Nicorandil had a significantly more potent relaxant effect in the proximal compared to the distal arterial rings contracted with 85 mM K+. Pretreatment with methylene blue (10(-5) M) did not significantly influence the regional difference in the action of nicorandil. Amlodipine (10(-9)-10(-6) M) had a significantly more potent and effective inhibitory and relaxant effect than nicorandil under the same conditions. In contrast to nicorandil, the effect of amlodipine was more prominent in the distal compared to the proximal vessel rings. The cumulative addition of extracellular Ca2+ exhibited a more potent contractile response in the distal rather than in the proximal rings. Nicorandil totally and amlodipine partly eliminated the contractile responses to the lowest concentration of Ca2+. The inhibitory effect of amlodipine on the contractile responses to higher Ca2+ concentrations was more pronounced than that of nicorandil. The results show that there are regional differences in the responsiveness of porcine coronary arteries to Ca2+, nicorandil and amlodipine. Our findings indicate that the regional difference in nicorandil-induced vasodilation was caused neither by the K(+)-channel opening nor by the nitrate-like mechanism of action, but could be due to a direct Ca(2+)-influx blocking effect of the drug.

Amlodipine↗
PubMed1998

Animal experimental implantation of an atrial septal defect occluder system.

OBJECTIVE: To establish the implantation technique for the atrial septal defect occluder system (ASDOS) device in an experimental animal model and to determine long term mechanical stability of the device and its in vivo properties in terms of biocompatibility and tissue reaction. MATERIALS AND METHODS: An atrial septal defect was created and the device implanted in 17 pigs (mean weight 30 kg). The implantation technique was refined and modified because of initial technical and anatomical complications during nine acute pilot studies. The technique proved to be feasible in eight subsequent survival studies. Four pigs were electively killed three months after implantation (group 1). The remaining four pigs were killed six months after implantation (group 2). RESULTS: Necropsy showed all devices were embedded in soft tissue three months after implantation. Microscopic examination of atrial septal tissue showed an acute granulomatous inflammatory reaction in group 1 and fibrosis in group 2. The intensity of the inflammatory reaction around the device was clearly milder in group 2, indicating a decline in the inflammatory response with time. Clinical and biochemical investigations indicated acceptable biocompatibility of the device. CONCLUSION: The implantation technique for the ASDOS device in a chronic pig model has been established. Biocompatibility of the device was acceptable.

Animals↗
PubMed1998

Relation between zero-stress state and branching order of porcine left coronary arterial tree.

The left common coronary arterial trees of eight pig hearts were dissected. The zero-stress state (the state of the organ when the external loads are removed) of the coronary arteries was determined by first cutting the arteries into short, ring-shaped segments perpendicular to the longitudinal axis of the blood vessel and then making a radial cut. This procedure caused the ring to open into a sector whose opening angle (theta), internal and external lengths (circumferences), and wall thickness were measured. Morphometric and theta data were organized in the framework of a diameter-defined Strahler system. We investigated 4 rings from the left common coronary artery (LCCA), 185 from the left anterior descending artery (LAD) and its branches, and 159 from the left circumflex artery (LCX) and its branches. The inner circumferences of the rings ranged over six orders for the LAD arterial tree and five orders for the LCX arterial tree, corresponding to a diameter range of about one order of magnitude for both arteries. theta demonstrates viscoelastic behavior and was measured 30 min after cutting. Our results show that the inner and outer circumference and the wall thickness increase as geometric sequences with the order number. theta is found to decrease linearly toward the smaller orders with a slope of 7.3 degrees/order in the range of the six largest orders. Strain calculations showed that the inner part of the arterial wall is in compression, whereas the outer part of the wall is in tension in the no-load (zero transmural pressure) state. This study provides basic data on the zero-stress state that are necessary for understanding the mechanics of the coronary artery.

Animals↗
PubMed1997

Myocardial insulin resistance in patients with syndrome X.

Insulin resistance is common in patients with angina pectoris, a positive exercise electrocardiogram, and normal coronary angiograms (syndrome X). It is still not known whether insulin resistance affects the cardiac muscle itself and, if so, whether insulin resistance involves myocardial hemodynamics and energy metabolism. We investigated hemodynamics as well as metabolite exchanges across the heart and the forearm in eight patients with syndrome X and eight control subjects during a baseline period after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Myocardial hemodynamics and metabolism were studied at rest, during pace stress, and in the recovery period after pacing. Neither coronary sinus blood flow nor forearm blood flow differed between the groups before and during the clamp. Whole body insulin-stimulated glucose uptake was decreased in the patients (15.6+/-2.1 vs. 23.1+/-2.0 micromol x kg-1 x min-1). Insulin-stimulated glucose uptake in the forearm and the cardiac muscle was equally reduced in the patients (46+/-5 and 48+/-5%). Myocardial glucose uptake correlated with total arterial delivery in the control subjects (r = 0.63, P < 0.01), but not in patients (r = 0.22, P = 0.13). Carbohydrate and lipid oxidation was similar in the two groups at rest, and changes during the clamp were not different in control subjects and patients either at rest, during pacing, or in the recovery period. Patients with syndrome X exhibit myocardial insulin resistance, but cardiac energy metabolism remains unaffected. In patients with syndrome X, insulin-stimulated glucose uptake is independent from myocardial blood flow.

Blood Glucose↗
PubMed1997

Impact of impaired coronary flow reserve and insulin resistance on myocardial energy metabolism in patients with syndrome X.

To evaluate the role of a decreased coronary flow reserve in the genesis of angina pectoris in patients with syndrome X, we studied myocardial hemodynamics and metabolism at rest, during pace stress, and in the recovery period after pacing in 18 consecutive patients with syndrome X and in 10 control subjects. By means of positron emission tomography or the intracoronary flow-wire method, patients were subclassified as having microvascular angina (MA, n = 8) when coronary flow reserve was reduced (<2.5) or no microvascular angina (non-MA, n = 10) when coronary flow reserve was preserved (> or =2.5). At rest, coronary sinus blood flow was increased in MA patients. During pace stress, coronary sinus blood flow increased by 39 +/- 6% in MA patients versus 67 +/- 12% in non-MA patients and 69 +/- 7% in controls (p <0.05). Patients with non-MA revealed fasting hyperinsulinemia, increased arterial concentration of free fatty acids, and a similar tendency for beta-hydroxybutyrate. Oxygen extraction and carbon dioxide release did not differ between groups. Net myocardial lactate release was not observed in any patient during pace stress and myocardial energy metabolism was preserved in all patients with syndrome X. During pacing, myocardial uptake of free fatty acids and beta-hydroxybutyrate was increased in non-MA patients. Myocardial uptake of free fatty acids correlated positively and myocardial glucose and lactate uptake correlated inversely with arterial concentrations of free fatty acids in all subjects. Metabolic evidence of myocardial ischemia is uncommon in patients with syndrome X, irrespective of a globally reduced coronary flow reserve. Although patients with syndrome X can be subclassified according to presence of a microvascular or a metabolic disorder, angina pectoris and ST-segment depressions coexist with a preserved global myocardial energy efficiency in all patients.

Cardiac Pacing, Artificial↗
PubMed1997

[Percutaneous transvenous balloon dilatation of mitral valve stenosis].

In this study, 42 consecutive symptomatic patients (median age 60 (30-78) years, 86% females) with mitral valve stenosis (57% had severely deformed and/or calcified mitral valves) were treated with (Inoue) balloon dilatation during the period August 1989-June 1994. Mitral valve area and cardiac output increased by 67 and 25%, whereas the transmital gradient as well as pulmonary artery pressure fell by 45% and 21%, respectively, after the dilatation. Follow-up at a mean of 16 (1-46) months revealed a total mortality of 12% (cardiac mortality of 7%). Five patients developed significant' mitral regurgitation after the treatment and four of these had subacute mitral valve replacement. A further four patients received an artificial valve during the follow-up period. During the follow-up period the increase in valve area remained unchanged, and accordingly 97% of the patients were in New York Heart Association functional class I-II. Balloon dilatation was an acceptable treatment in the described elderly population with significant mitral stenosis and deformed valves.

Adult↗
PubMed1997

Effect of verapamil in intermittent claudication A randomized, double-blind, placebo-controlled, cross-over study after individual dose-response assessment.

BACKGROUND: The calcium antagonist verapamil is a vasodilator drug that has been shown to increase oxygen extraction of ischemic tissues in coronary and peripheral vascular disease. METHODS AND RESULTS: Since the balance between the positive and the negative effects of vasodilation may be delicate in ischemic diseases a dose-response study (dose range, 120 to 480 mg) was established to determine optimal, individual dosages of slow-release verapamil in 44 patients with stable intermittent claudication (Fontaine classification stage II) with respect to walking capacity. A randomized, double-blind, placebo-controlled, cross-over study (4 weeks) was performed to assess clinical and hemodynamic effects of verapamil. The optimal daily dose of verapamil on maximal walking ability was 120 (8 patients), 240 (8 patients), 360 (14 patients), and 480 mg (14 patients). Walking distances were measured at a metronome-controlled speed of 60 steps per minute on level surface. Optimal individual doses of verapamil increased mean pain-free walking distance by 29% from 44.9 to 57.8 meters (P < .01) and maximal walking distance by 49% from 100.7 to 149.8 meters (P < .001) compared with placebo. The increase in maximal walking distance correlated positively only with initial systolic ankle pressure (r = .49, P < .001) and ankle/brachial pressure index (r = .37, P < .013). Verapamil had no effect on systolic ankle pressure, ankle/brachial pressure index, peripheral leg temperature, or blood pressure, which suggests that the drug may have extrahemodynamic effects, possibly brought about through improved oxygen metabolism. CONCLUSIONS: Verapamil showed significant clinical benefits in patients with moderate intermittent claudication in this short-term study. Individual optimization of drug dosage should be considered an option both in trials and in the clinical setting in these patients.

Aged↗
PubMed1997

Insulin resistance in cardiac syndrome X and variant angina: influence of physical capacity and circulating lipids.

Insulin resistance has been demonstrated in patients with angina pectoris irrespective of detectable atherosclerosis at coronary angiograms. We compared insulin sensitivity, lipid profiles, and exercise capacity in 20 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls to investigate whether the presentation of the insulin resistance syndrome differs between the two patient groups with disparate vascular abnormalities. All patients had angiographically normal coronary arteries. Maximal oxygen uptake (VO2 max) was determined at bicycle exercise testing. Insulin sensitivity (SI) was assessed by the minimal model analysis of the intravenous glucose tolerance test. Patients with variant angina had significantly lower VO2 max than controls (mean +/- SE, 25.6 +/- 1.5 vs 30.6 +/- 1.4 ml x kg-1 x min-1, p < 0.05), whereas VO2 max in patients with syndrome X was intermediate (27.1 +/- 1.3 ml x kg-1 x min-1). Compared with controls, patients with syndrome X and variant angina had reduced insulin sensitivity (controls, 1.47 +/- 0.16 10(-4) x min-1/per pmol/L vs syndrome X, 0.86 +/- 0.11 10(-4) x min-1 per pmol/L and variant angina, 0.96 +/- 0.15 x 10(-4) x min-1 per pmol/L; analysis of variance, p < 0.05). Only patients with syndrome X exhibited fasting hyperinsulinemia. Patients with syndrome X also had higher fasting concentrations of triglycerides and total cholesterol and lower concentrations of high-density lipoprotein cholesterol than controls. When adjusting SI for variances of VO2 max, differences in SI vanished between controls and patients with variant angina but not between controls and patients with syndrome X. Thus syndrome X and variant angina are both associated with insulin resistance, but lipid abnormalities are only prominent in patients with syndrome X. A variable expression in terms of concomitant disturbances of lipid profiles and disparate influences of physical capacity suggests different underlying mechanisms.

Angina Pectoris, Variant↗
PubMed1997

Effects of ranolazine on ischemic threshold, coronary sinus blood flow, and myocardial metabolism in coronary artery disease.

Cytoprotection or metabolic modulation is a new principle in the treatment of angina pectoris. The effect of ranolazine (a cytoprotective drug) on ischemic threshold, coronary sinus blood flow, and myocardial metabolism was evaluated by means of two pacing sequences in nine male patients with coronary artery disease (CAD) and in eight male controls. Ranolazine was given as an intravenous bolus followed by continuous infusion; the mean total dose was 32.7 mg and 31.7 mg in patients and controls, respectively. Angina pectoris was relieved in two patients after ranolazine but pacing time to pain was unchanged in the remaining patients. Maximal ST depression was lower (p = 0.02), but pacing time to maximal and to 1-mm ST depression remained unchanged after the drug. Ranolazine had no overall influence on coronary sinus blood flow, cardiac oxygen consumption, blood pressure, and heart rate. Cardiac uptake of free fatty acids (FFA) was reduced (p = 0.01), and net uptakes of glucose (p = 0.07) and lactate (p = 0.06) tended to be lower after ranolazine in CAD patients and controls. Ranolazine had no direct influence on cardiac exchange of glutamate, alanine, and citrate or on the arterial concentration of any metabolite. In the present study ranolazine had minimal clinical effects. A decrease in myocardial FFA utilization, however, allows greater myocardial glucose oxidation, which may increase the energy production in relation to oxygen availability.

Acetanilides↗
PubMed1997

Impaired human coronary artery distensibility by atherosclerotic lesions: a mechanical and histological investigation.

The objective of this study was to evaluate the relationship between human coronary artery distensibility and vessel wall morphology assessed by histomorphometry. Coronary artery pressure-cross-sectional area relations and distensibility were studied in excised autopsy hearts by means of a balloon-based impedance planimetric technique 2 cm from the aortic orifice of the arteries. Later the hearts were perfusion fixed at 100 mm Hg and cross-sectioned 17, 20 and 23 mm distal to the aortic orifice. The areas of lumen, intima and media were measured. Nineteen left anterior descending coronary arteries (LAD) and 15 right coronary arteries (RCA) from 25 hearts (12 women and 13 men) were investigated. The age of the subjects was 48-97 years (mean 73.8 years). Non-linear relations were found between balloon pressure and coronary cross-sectional area (according with the function y = a + bx0.5) and between balloon pressure and coronary distensibility, but there were no differences in these relations between the LAD and RCA. Subjects' age was positively correlated with wall thickness (r = 0.44, P < 0.05), intima area (r = 0.46, P < 0.01) and media area (r = 0.44, P < 0.05) of the coronary arteries. Additionally, the distensibility at low pressures was inversely correlated with arterial wall thickness (r = -0.37, P < 0.05). When focusing only on arteries with concentric atherosclerotic lesions, distensibility at low pressures was inversely correlated with arterial wall thickness (r = -0.57, P = 0.01) and intima area (r = -0.53, P < 0.05). Arteries with concentric lesions were less distensible at low pressures compared with arteries having eccentric lesions (5.4 +/- 0.8.10(-2) vs. 3.6 +/- 0.7.10(-2) kPa-1, P < 0.05) but this difference was absent at higher pressures. No difference in coronary artery distensibility was found between men and women. Age and distensibility were not correlated. These findings may have in vivo implications for complications to angioplasty procedures such as recoil and restenosis.

Aged↗
PubMed1997

Cardiac function during iron chelation therapy in adult non-thalassaemic patients with transfusional iron overload.

It is well-documented that iron chelation by desferrioxamine protects/improves the cardiac function in blood transfusion-dependent children suffering from beta-thalassaemia. In patients who do not become dependent upon blood transfusion until adulthood (ANT-patients), iron chelation by desferrioxamine may affect the cardiac function in unknown ways, presumably because age-related changes in the heart may cause iron chelation to affect the cardiac function in different ways. We therefore followed the left ventricular ejection fraction (LVEF) by multigated radionuclide angiography in 16 iron-loaded ANT-patients during iron chelation alone and after increasing the efficacy of chelation by vitamin C supplementation. During 12 months of iron chelation the mean LVEF fell significantly from 63.3% to 58.0% (p=0.04). Individual changes in LVEF did not correlate significantly with age but with the pretreatment liver iron concentration. After initiation of vitamin C supplementation, the mean LVEF increased from 55.9% to 65.3% (p=0.01). Our data suggest that in ANT-patients prolonged desferrioxamine treatment without vitamin C supplementation may be associated with reduced LVEF, whereas vitamin C supplementation seems to benefit the cardiac function. Similar findings have not been described in beta-thalassaemia and may hence be specific for ANT-patients. However, our findings have to be confirmed by controlled studies.

Adolescent↗
PubMed1997

Haemodynamic and metabolic effects of gallopamil as additive to calcium-containing and calcium-free cardioplegic solutions in mature pig hearts.

Myocardial haemodynamic and metabolic effects of the calcium-channel blocker gallopamil as additive to calcium-containing (St Thomas Hospital, STH) and calcium-free (Bretschneider procaine-containing, BRT) crystalloid cardioplegic solutions were evaluated. Adult pig hearts (weight 0.033 kg) were randomized to four groups and perfused with 1 litre of cold (4 degrees C) cardioplegic solution; group A: BRT without gallopamil, n = 9, group B: BRT with gallopamil (0.4 microM), n = 8, group C: gallopamil-free STH, n = 8, and group D: STH with gallopamil (0.4 microM), n = 8. After storage at 4 degrees C for 6 hours the hearts were reperfused with blood/Ringer solution in a modified Langendorff model for 60 min. Developed left ventricular pressure, rate-pressure product and +dP/dt were lower in gallopamil-treated hearts during reperfusion (p < 0.05), as were oxygen extraction and oxygen uptake (p < 0.05) and lactate release (p < 0.05). Myocardial blood flow was greater in gallopamil-treated hearts (p < 0.05). In hearts comparable in size and anatomy to the human heart, gallopamil added to both cardioplegic solutions reduced cardiac function and oxygen uptake despite increased myocardial blood flow. The findings suggest reduced myocardial protection after addition of gallopamil to cardioplegic solutions.

Animals↗
PubMed1996

[Angiopeptin versus placebo for reductin of restenosis after PTCA treatment. A randomized, double-blind study].

Angiopeptin, a somatostatin analogue, inhibits intimal hyperplasia after (percutaneous transluminal coronary angioplasty) (PTCA) in several animal models. This pilot study sought to determine the effect of subcutaneous infusion of angiopeptin on clinical events and restenosis in patients undergoing successful PTCA. One hundred and twelve patients were randomized to receive continuous subcutaneous angiopeptin (750 micrograms/day) or placebo infusion from the day before PTCA and for the following four days in a double-blind study. Eighty patients had a successful PTCA, and 75 of these patients with 94 lesions underwent angiography 6 +/- 2 months after PTCA. All 112 patients underwent clinical follow-up at 12 months. The 12-month event rate (death, myocardial infarction, coronary artery bypass grafting and re-PTCA) was reduced from 34% to 25% (p = 0.30) by angiopeptin by intention to treat analysis. Restenosis (> or = 50% diameter stenosis) was significantly reduced in lesions treated with angiopeptin (12% vs 40%; p = 0.003). Late lumen loss was also significantly reduced after angiopeptin treatment (0.12 +/- 0.46 mm vs 0.52 +/- 0.64 mm; p = 0.003). In conclusion, continuous subcutaneous angiopeptin infusion for five days tended to decrease clinical events and restenosis after PTCA.

Adolescent↗
PubMed1996

[Esophagoscopy in patients with angina pectoris and normal coronary arteriography].

The clinical value of oesophago-gastro-duodenoscopy and distal oesophageal biopsies was investigated in 49 patients with angina pectoris and normal coronary angiograms. The results were compared to 24 hour oesophageal pH-monitoring of the patients and of a control group of 22 healthy sons. Macroscopic esophagitis--mainly grade I was found in 31% of the patients and microscopic oesophagitis in 25%. The only major abnormalities were the identification of three peptic ulcers (6%). Median (range) reflux index was 1.3 (0.0-13.4) in the patient group and 2.1 (0.0-9.9) in the controls (p = 0.49). There were no differences with respect to endoscopical findings or reflux index between patients with a positive and patients with a normal exercise electrocardiogram. At a median 36 months post study 38% of the patients had undergone acid secretion inhibitor treatment with an effect on symptoms in only 4%. The study provides evidence that routine oesophago-gastro-duodenoscopy is of limited value in this patient group.

Adult↗