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Biomedical subjects

J P Bagger

Publications and source records attributed to J P Bagger.

At least 109 records · Page 6Linked to original sources
PubMed1985

Reproducibility of coronary haemodynamics and cardiac metabolism during pacing-induced angina pectoris.

The reproducibility of coronary sinus blood flow (CSBF) (thermodilution technique) and myocardial metabolism (exchange of oxygen, lactate, free fatty acids, glucose, citrate, glutamate and alanine) during two identical pacing periods separated by 45 min were studied in eight patients with chronic coronary artery disease. The mean of the individual difference (delta-values) between values during the first (T1) and second (T2) test, at corresponding times (rest, pacing and after 3-5 min of recovery), were calculated and expressed as a percentage of the resting level of each parameter in order to assess their reproducibility. All patients experienced angina pectoris during both pacing sessions, and pacetime to onset of symptoms did not differ between the tests. Group values for haemodynamics and exchange of metabolites were acceptably reproducible throughout the period under study. Mean delta-values of CSBF ranged from 10% to 16% and myocardial oxygen uptake from 14% to 22% in relation to the resting levels. In contrast, mean delta-values of metabolites ranged from 5% to 136% in relation to the respective A-V differences during the study. The greatest variation occurred during pacing and of all the metabolites lactate exchange varied most. A spontaneous variation in the degree of ischaemia during repeat stress tests might be the major reason for the metabolite variability. Changes in CSBF, however, tended to correlate inversely to the delta-aortocoronary sinus differences of substrates during pacing. Precision of chemical analysis and blood sampling technique were of minor importance for the variability. Since lactate exchange varied most, the study suggests that additional measurements should be made of more metabolites when assessing the efficacy of therapy by means of myocardial metabolism.

Adult↗
PubMed1985

Myocardial changes in rats with lithium-induced uraemia.

The possible effects of lithium on myocardial morphology were studied at the light-microscopic level in three different rat models: (i) rats with chronic renal failure due to lithium administration for 8-16 weeks after birth, (ii) normal, adult rats treated with lithium for 16 weeks, and (iii) new-born rats exposed to lithium in their prenatal life. Morphological changes were found in 57% of the male rats with lithium-induced uraemia after lithium administration for 16 weeks postnatally. The changes comprised myocytic degeneration and necrosis associated with infiltration of lymphocytes, histiocytes and plasma cells. This morphological picture is different from the myocardial changes associated with chronic renal failure. Male rats with chronic uraemia after withdrawal of lithium 8 weeks postnatally showed no myocardial changes after 16 weeks. Also, male rats with normal renal function had no myocardial changes after 16 weeks on lithium, but these rats had a significantly lower plasma level of lithium than the lithium-uraemic rats (0.8 vs. 1.4 mmol/l). It is suggested that myocarditis was a consequence of persistent high plasma levels of lithium maintained in the lithium-uraemic rats and that cardiotoxic effects of lithium may be potentiated by concomitant renal failure.

Animals↗
PubMed1984

Beneficial effect of a low-fat low-calorie diet on myocardial energy metabolism in patients with angina pectoris.

8 patients with exertional angina pectoris were treated for 3 months with a low-fat, low-calorie diet. Serum cholesterol was reduced by 28% and body-weight by 7.9 kg on average. The effect of the dietary intervention was assessed by a heart metabolic study during pacing-induced tachycardia. After dietary treatment coronary sinus blood-flow and myocardial oxygen consumption were considerably reduced, but pacing time before angina developed increased. Other improvements were a reduction in lactate release during pacing, a reduction in citrate release during recovery, a reduction in alanine output during rest and recovery, and a lower uptake of glutamate. The results suggest a beneficial effect of low-fat, low-calorie dietary treatment on myocardial energy metabolism in patients with exertional angina pectoris.

Alanine↗
PubMed1984

Myocardial exchange of metabolites after nitroglycerin in patients with coronary artery disease.

We studied the effects of sublingual nitroglycerin (dose range 0.5-1.0 mg) on cardiac metabolism in the resting state in 12 patients with chronic coronary artery disease. Seven patients with chronic coronary artery disease served as a control group. No patient from either of the groups experienced angina pectoris during the study. Reduced heart work after nitroglycerin was evident from a 34% decrease of oxygen uptake (P less than 0.001) and a 35% fall in coronary sinus blood flow (P less than 0.01). Nitroglycerin decreased lactate extraction by 30% (P less than 0.05), lactate uptake by 58% (P less than 0.025); glucose uptake by 47% (P less than 0.01) while net exchange of free fatty acids did not change. The aorto-coronary sinus difference of plasma citrate became increasingly negative (from -4 +/- 3 mumol/l to -8 +/- 2 mumol/l) (P less than 0.02) after nitroglycerin. In the control group coronary sinus blood flow and myocardial exchange of oxygen and substrates remained unchanged. Our results suggest a relatively increased myocardial utilization of free fatty acids compared with that of carbohydrates after nitroglycerin. This may in part be explained as an inhibition of glycolysis due to citrate accumulation. The study indicates that myocardial lipid-carbohydrate metabolism is disturbed in chronic coronary artery disease even in patients without clinical evidence of ischaemia in resting state and that nitroglycerin reverses this condition towards the metabolism of the normal heart.

Blood Glucose↗
PubMed1984

Intracardiac electrography in patients before and after surgical repair of secundum atrial septal defect.

Nine patients (mean age 32 years, range 9-58) with a secundum atrial septal defect (ASD) were investigated by intracardiac electrography before and, on an average, 14 months after circumclusion of the defect. Postoperatively, four patients developed atrial fibrillation or flutter requiring treatment. After the repair, sinus node recovery time and the H-V interval increased significantly. The P-A interval, the A-H interval, sinoatrial conduction time, and the effective refractory period of the atrium (ERPA) remained unchanged. In the patients who developed atrial tachyarrhythmias, the mean preoperative ERPA was significantly longer than in the remaining patients; in patients with ERPA less than 220 ms, no atrial arrhythmias occurred. Our findings suggest that circumclusion of a secundum ASD has a sustained deleterious effect on sinus node function and His-Purkinje conduction. Preoperative determination of ERPA might be of value for the prediction of postoperative atrial arrhythmias in patients submitted to ASD repair.

Adolescent↗
PubMed1984

Prevalence of vasospastic ischaemia induced by the cold pressor test or hyperventilation in patients with severe angina.

We performed coronary artery spasm provocation, using the cold pressor test (CPT) and hyperventilation (HVT) in 105 patients (87 males, 18 females) with mean age 51.9 years (range 25-69) consecutively admitted for coronary angiography due to attacks of chest pain. A positive response to spasm provocation (ST segment elevation or depression greater than or equal to 0.1 mV or pseudonormalization of negative T-waves) was seen in 25 patients (23.9%) (group A), with 8 patients responding to CPT and 23 to HVT. In the remaining patients (group B) a negative response was found. Of 80 patients with coronary artery stenosis (diameter reduction greater than 50%), 22 (27.5%) showed a positive response. During CPT and HVT the rate pressure product increased 25% and 16%, respectively in group A versus an increase of 139% during exercise testing in the same patients. This suggests that ischaemia induced by CPT or HVT is not caused by increased myocardial oxygen demand. Repeat spasm provocation was performed during coronary angiography in 14 patients from group A and 14 from group B. The induced reduction in the diameters of the ischaemia related vessels was on average 48.3% in group A versus a 9.9% reduction of the left anterior descending artery in the patients from group B (P less than 0.01). In group A 88% had a history of nocturnal angina versus 38.8% in group B (P less than 0.001). A positive exercise test was found in 87% and 35.6% in group's A and B respectively (P less than 0.0005).

Adult↗
PubMed1984

Myocardial glutamate and alanine exchanges related to carbohydrate metabolism in patients with normal and stenotic coronary arteries.

Myocardial exchanges of glutamate, alanine, glucose, lactate, free fatty acids (FFA) and oxygen in resting state were determined in nine subjects (controls) without and in 28 patients with coronary artery disease (CAD). Patients with CAD showed increased myocardial glutamate uptake (2.51 +/- 0.60 mumol/min) and alanine release (1.25 +/- 0.60 mumol/min) compared to controls (glutamate uptake: 1.66 +/- 0.79 mumol/min; alanine release: 0.63 +/- 0.41 mumol/min). Myocardial glucose and lactate uptake was augmented in CAD patients, whereas FFA arteriovenous differences were decreased in patients with three-vessel-disease. The amount of glutamate taken up by the heart correlated positively to lactate uptake in all subjects (r = 0.84) and to external glucose utilization in patients with CAD (r = 0.72). Myocardial alanine release was positively related to glucose and lactate uptake in controls and in patients with only moderate CAD (one-vessel-disease). Glucose and FFA uptake correlated inversely in controls (r = 0.84), but not in CAD patients. A tight relation between exchanges of glutamate/alanine and carbohydrate metabolism in human heart is demonstrated. The data suggest altered myocardial substrate exchange towards augmented carbohydrate utilization in CAD patients in resting state. The results agree with in vitro and animal studies suggesting extraction of glutamate from the circulation to be of importance for maintaining carbohydrate consumption in chronic ischaemic heart disease.

Adult↗
PubMed1984

HV interval in calcific aortic stenosis. Relation to left ventricular function and effect of valve replacement.

Intracardiac electrography and 24 hour ambulatory electrocardiographic monitoring were carried out in 20 patients with calcific aortic stenosis (mean pressure gradient 86 mm Hg) to investigate (a) the role of bradycardia and tachycardia in the pathogenesis of syncope in aortic stenosis, (b) the relation between haemodynamic data and electrophysiological abnormalities, and (c) whether valve replacement corrects electrophysiological abnormalities. Intracardiac electrograms showed impaired sinus node function in five patients and a prolonged HV interval (greater than or equal to 50 ms) in 11 but there was no difference in the findings of 13 patients with syncope and seven without. Ambulatory monitoring showed short pauses in three patients and brief episodes of tachycardia in four, but there was no difference in the findings of patients with and without syncope. The HV interval correlated inversely with the left ventricular ejection fraction, whereas no correlation was found between the HV interval and the pressure gradient. Nine patients were re-evaluated 15 months after aortic valve replacement. No change was found in sinus node function, but the HV interval had increased by 7.8 ms. It is concluded that in calcific aortic stenosis neither bradycardia nor tachycardia is shown to be a frequent cause of syncope, a prolonged HV interval is a frequent finding and further prolongation occurs after valve replacement, and contractility and conductivity appear to deteriorate in parallel.

Adult↗
PubMed1984

Cardiomyopathy in western Denmark.

A retrospective study was carried out to assess the incidence of cardiomyopathy in western Denmark (Jutland and Funen) (population 2 798 000) during a two year period (1980-81). The WHO/ISCF classification was strictly followed, and rigid criteria for exclusion and inclusion of patients were adopted. Thus cases in which specific heart muscle disorders (myocarditis, alcoholic heart disease, hypertension etc) were merely suspected were excluded. Forty one patients had dilated cardiomyopathy (overall incidence 7.3/10(6) population/year) and 20 hypertrophic cardiomyopathy (overall incidence 3.6/10(6) population/year). In men aged 40-59 years the occurrence of dilated cardiomyopathy was 23.4/10(6) population/year. Only one case of Löffler's endomyocardial disease was diagnosed during the study period. Since the investigation was retrospective and was a study of diseased persons and not a population, and since a specific set of criteria for exclusion and inclusion was rigidly applied, the results represent the minimum frequency of these diseases.

Adolescent↗
PubMed1983

Myocardial exchanges of glutamate, alanine and citrate in controls and patients with coronary artery disease.

1. Myocardial exchanges of plasma alanine, glutamate, citrate, lactate, glucose and free fatty acids were determined in 17 patients with coronary artery disease and in seven control subjects during rest, atrial pacing and recovery. 2. Myocardial release of alanine was demonstrated in all subjects. The amount released was higher in patients with coronary artery disease than in controls. In the patients alanine release was related to severity of coronary artery stenosis. 3. All subjects showed myocardial uptake of glutamate, higher in patients than in controls at rest and during recovery. During atrial pacing myocardial glutamate extraction remained unchanged in controls but decreased in patients. 4. Citrate was released by the heart in all controls and patients. During recovery citrate output was higher in patients than in controls. 5. Myocardial alanine and citrate release during recovery were positively correlated. Both were positively related to myocardial uptake of glutamate during recovery and to the decrease in glutamate extraction during pacing. 6. The results indicate changed myocardial citrate and amino acid metabolism in coronary artery disease. Measurement of myocardial exchanges of glutamate, alanine and citrate in addition to lactate is suggested as a sensitive biochemical test in assessing myocardial ischaemia in man.

Aged↗
PubMed1983

The effect of verapamil on myocardial exchange of free fatty acids, citrate, lactate and glucose in coronary artery disease.

Twelve patients with coronary artery stenosis (greater than 50% diameter reduction) underwent two identical periods of atrial pacing before and after i.v. verapamil (0.1 mg/kg). Myocardial exchanges of free fatty acids (FFA), citrate, lactate and glucose were evaluated from measurements of arterio-coronary sinus differences (n = 12) and coronary sinus blood flow (CSBF) (n = 9). Before verapamil 11 patients developed angina. Verapamil abolished pain in seven and improved pacing time to angina in four patients. After verapamil, aortic pressure decreased (P less than 0.05), while the rate pressure product remained unchanged during rest and pacing. Verapamil decreased CSBF by 20% (P less than 0.05) during pacing, and increased oxygen extraction both during pacing and recovery. During pacing verapamil increase net FFA extraction (P less than 0.01) and uptake (1 to 8 mumol/min P less than 0.05), and decreased glucose extraction (P less than 0.05) and uptake (22 to 11 mumol/min P less than 0.02. Verapamil increased myocardial citrate release during pacing (P less than 0.05), suggesting a citrate inhibition of glycolysis as a possible mechanism of the inhibited glucose uptake. During pacing, verapamil reduced lactate release in seven patients (P less than 0.05) and decreased lactate extraction in five patients (P less than 0.05). The results suggest that verapamil mediates its beneficial effect on pacing-induced angina, in part by changing substrate utilization of the ischaemic myocardium in man towards that of normal heart.

Adult↗
PubMed1983

Increased coronary sinus lactate concentration during pacing induced angina pectoris after clinical improvement by glyceryl trinitrate.

Ten patients with stable angina pectoris and obstructed coronary arteries (greater than 75% reduction in diameter) were studied before and during two periods of pacing, the second of which was preceded by sublingual administration of glyceryl trinitrate (mean dose 0.78 mg). Coronary sinus blood flow measurements and aortocoronary sinus blood sampling for metabolite determinations were carried out. Although the rate of pacing was increased by 10 beats/minute after glyceryl trinitrate administration, the onset of angina was delayed in eight patients during pacing. Drug administration decreased coronary sinus blood flow by 42% and myocardial oxygen uptake by 41% during pacing and induced a shift in mean lactate extraction towards a net release (from 3.1% to -12.6%). It increased the number of patients producing lactate from three to five. Glyceryl trinitrate administration decreased myocardial glucose uptake throughout the study, decreased lactate extraction during recovery, and increased the aortocoronary sinus citrate gradient at rest and during recovery, while the exchange of free fatty acids remained unchanged. A decrease in aortocoronary sinus lactate difference during pacing after glyceryl trinitrate administration correlated positively with the fall in coronary sinus blood flow. The metabolic data do not indicate an augmented myocardial lactate production after glyceryl trinitrate administration. A decrease in coronary sinus blood flow seems, therefore, to be of primary importance in explaining the elevated coronary sinus lactate concentration. Our finding that coronary sinus lactate concentration increased during pacing after glyceryl trinitrate administration despite clinical improvement questions the validity of its use as a quantitative index of ischaemia.

Adult↗
PubMed1981

Circadian plasma citrate rhythms in juvenile diabetics.

Postabsorptive plasma concentrations of citrate, glucose, lactate, free fatty acids (FFA), ketone bodies and free insulin were measured once weekly for 5 weeks in 18 male juvenile diabetics. The circadian rhythms of the same substances were followed in 12 male diabetics. In 8 of them, daily rhythms were measured twice, before and after plasma glucose was lowered by increasing insulin doses. In the postabsorptive state, the mean plasma citrate concentration of the diabetics, 117 mumol/l (range 65--160), did not differ from that of non-diabetics despite two- to threefold higher levels of plasma glucose, FFA and ketone bodies in diabetics. Daily plasma citrate profile in diabetics showed peak concentrations in the morning and late afternoon. Citrate level throughout the day fell after increased insulin administration, whereas the diurnal pattern remained unchanged. Both the week-to-week coefficient of variation (mean 10%) and the diurnal coefficient of variation (mean 17%) of plasma citrate were below those of any other substances measured (p less than 0.001). Postabsorptive citrate concentration correlated negatively to the diurnal variation of plasma glucose whether diabetic control was apparently good or poor. The results support the idea that plasma citrate level reflects intracellular citrate regulation of glucose utilization. In spite of an interindividual range of 100%, individual citrate level was remarkably constant. Postabsorptive plasma citrate concentration is proposed as a control marker of lability of circulating glucose in insulin-treated diabetics.

Adolescent↗
PubMed1981

Myocardial release of citrate and lactate during atrial pacing-induced angina pectoris.

Arterio-coronary sinus (A-Cs) differences of plasma citrate, glucose, free fatty acids and blood lactate were measured in 19 patients with coronary artery disease (CAD) and in eight control subjects exposed to atrial pacing. Among patients with CAD 11 showed a myocardial release of lactate during pacing (lactate producers, LP) while myocardial lactate extraction was unchanged in the remaining eight patients (lactate non-producers, LNP). In patients with CAD, (A-Cs) plasma citrate differences became increasingly negative during recovery from pacing, values at rest and at 3-5 min of recovery were: -5 +/- 2 mumol/l (mean +/- SD) vs. -12 +/- 5 mumol/l in LP (P less than 0.001) and -6 +/- 3 mumol/l vs. -8 +/- 4 mumol/l in LNP (P less than 0.01). In controls, (A-Cs) citrate difference varied inversely, from -8 +/- 4 mumol/l at rest to -2 +/- 4 mumol/l at 3-5 min of recovery (P less than 0.001). An increasingly negative (A-Cs) plasma citrate difference during recovery from pacing-induced angina pectoris is suggested to reflect a wash-out of accumulated citrate from ischaemic heart cells; and is proposed as a more sensitive marker of ischaemia in man than a myocardial release of lactate.

Adult↗
PubMed1980

Myocardial citrate metabolism in control subjects and patients with coronary artery disease.

A significant release of citrate across the myocardium was demonstrated in twenty-two patients with coronary artery disease (CAD) and in ten control subjects in fasting resting state. In both groups, increasingly negative arterio-coronary sinus (A-Cs) plasma citrate differences correlated positively to arterial plasma free fatty acid (FFA)concentrations and negatively to (A-Cs) differences of plasma glucose. This supports the hypothesis that a citrate inhibition of glycolysis at the site of phosphofructokinase is of regulatory importance for myocardial glucose metabolism, and suggests that FFA supress glucose utilization by the heart in many by this mechanism. The capacity of plasma FFA to increase myocardial citrate release was significantly higher in controls than in patients with CAD, and was found to be positively related to myocardial capacity of oxygen consumption as estimated from the product of heart rate and systolic blood pressure during an exercise tolerance test.

Adult↗