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C W Flesche

Publications and source records attributed to C W Flesche.

14 recordsLinked to original sources
PubMed2004

Myocardial ferritin content is closely related to the degree of ischaemia.

AIM: Ferritin acts as an iron scavenger and thereby may reduce iron catalysed oxygen radical production during reperfusion injury. We tested the hypothesis that the myocardial ferritin concentration is enhanced during ischaemia in proportion to the blood flow reduction. METHODS: In 10 anaesthetized, open chest Beagle dogs (six controls and four with 60 min coronary occlusion) regional myocardial blood flow (RMBF) was measured with the tracer microsphere technique and ferritin was determined in samples with an average mass of 125 mg (124-256 samples per heart). RESULTS: Under physiological conditions heart rate was 88 +/- 12 bpm, mean aortic pressure 98 +/- 8 mmHg, and RMBF 0.99 +/- 0.33 mL min-1 g-1. Data did not differ between experimental groups, P > 0.05. In the control group regional myocardial ferritin concentration averaged 11.76 +/- 3.54 ng mg-1 protein and exhibited a significant blood flow independent heterogeneity (CV(biol) = 0.27). However, between low and high flow areas (relative flow <0.5 and >1.5 times the average RMBF, respectively) no significant difference in ferritin was found, P > 0.05. In four experiments, in which regional blood flow was reduced by 40% to 0.60 +/- 0.23 mL min-1 g-1, regional ferritin content was significantly higher as compared with the control group 27.95 +/- 6.16 vs. 11.76 +/- 3.54 ng mg-1 protein, respectively. An inverse relationship was observed between ferritin and RMBF, r = -0.61, P < 0.001. Thus, a reduction of RMBF of >80% was associated with a 2.75-fold increase of the average ferritin content. Between subepicardium and subendocardium no significant difference in ferritin content was observed, neither in the control group nor in the group with induced ischaemia. Regions with control low and high flow responded similarly to the coronary constriction with regard to the local ferritin concentration: 27.88 +/- 15.22 vs. 30.10 +/- 14.91 ng mg-1, P > 0.05, respectively. A data analysis using Baye's theorem indicated that sensitivities were 0.28 and 0.94 for average flow reductions of 5 and 93%. In additional in vitro measurements (ischaemic incubation at 37 degrees C) myocardial ferritin content increased almost linearly within the first 60 min of incubation and thereafter remained unchanged. CONCLUSIONS: (1). Local physiological ferritin content in myocardium is heterogeneous and unrelated to control myocardial blood flow. (2). Ischaemia results in an enhanced ferritin content in relation to the degree of ischaemia. (3). The increase of myocardial ferritin requires a severe degree of ischaemia.

Animals↗
PubMed1999

[How much blood flow is required by the myocardium?].

OBJECTIVES: The myocardium of the left ventricle exhibits spatial heterogeneity of blood flow under physiological conditions. This study was designed to investigate, whether oxygen supply is jeopardized in low flow areas (blood flow < 50% of mean) under physiological conditions and whether areas of high flow (> 150% of mean) exhibit perfusion in excess of demand ("luxury perfusion"). METHODS: The study was performed in anesthetized and ventilated beagle dogs. Local blood flow was reduced by mechanically narrowing of the r. circumflexus of the left coronary artery; myocardial blood flow was measured by the tracer-microsphere technique, free concentrations cellular adenosine by the SAH-technique, regional metabolism of substrates by the desoxyglucose-technique. RESULTS: Low flow areas exhibited normal oxygenation of the myocardium, while in high flow areas no luxury perfusion could be demonstrated. CONCLUSION: Myocardial blood flow and metabolism demonstrate significant spatial heterogeneity. There appears to be no absolute threshold of blood flow, where regional myocardial ischemia develops. Probably biochemical evidence of myocardial ischemia is determined by a local ratio of oxygen supply and demand.

Adenosine↗
PubMed1998

Coronary reserve of high- and low-flow regions in the dog heart left ventricle.

BACKGROUND: Left ventricular myocardial blood flow is spatially heterogeneous. The hypothesis we tested was whether myocardial areas with a steady-state flow <0.5 times mean flow are underperfused and areas with flow > 1.5 times mean flow are overperfused. METHODS AND RESULTS: In anesthetized beagle dogs (n=10), the relationship between local blood flow versus S-adenosylhomocysteine (SAH) concentration, a measure of the free intracellular adenosine concentration, and lactate, a measure of the myocardial NADH/NAD+ ratio, were determined under control conditions and after coronary constriction. Control local myocardial blood flow was 0.99+/-0.46 mL x min(-1) x g(-1), with a coefficient of variation of 0.36+/-0.12 (n=256 per heart; sample wet mass, 125+/-30 mg). Tissue concentrations of SAH (3.4+/-2.5 nmol/g) and lactate (1.88+/-0.80 micromol/g) were not elevated in low-flow samples. However, after coronary artery constriction, poststenotic blood flow decreased from 1.00+/-0.27 to 0.49+/-0.22 mL x min(-1) x g(-1) (P<0.04), with significant correlation between local SAH and flow (r=-0.59) and lactate and flow (r = -0.50). Although nearly all samples from control high-flow regions showed increased SAH concentrations if relative flow after stenosis was <1.0, control low-flow samples frequently displayed low SAH concentrations. The percent reduction in flow determined the changes in the local SAH and lactate concentration, independent of the local control blood flow. CONCLUSIONS: When the coronary inflow is unrestricted, the oxygen supply to control low-flow regions meets metabolic demand. Flow to control high-flow regions reflects a higher local demand rather than overperfusion. Thus, blood flow heterogeneity most likely reflects differences in aerobic metabolism.

Animals↗
PubMed1998

Regional myocardial heat-shock protein (HSP70) concentrations under different blood flow conditions.

The concentration of heat-shock proteins of 70 kD (HSP70) in heart tissue has been shown to increase during transient myocardial ischaemia and to persist during several hours of reperfusion. In this study the relationship between the local myocardial HSP70 concentration and blood flow was addressed for control physiological conditions and acute myocardial ischaemia. A specific aim of this study was to address the question of whether low flow areas under control physiological conditions have undergone a transient ischaemia during the preceding hours and thus may be in a state of hibernation or stunning. In 12 anaesthetized, open-chest beagle dogs (6 control and 6 with 60-min coronary artery stenosis) heart rate, mean aortic pressure, mean arterial partial pressure of O2 and partial pressure of CO2 averaged 85+/-16 beats/min, 94+/-14 mmHg, 102+/-17 mmHg and 39+/-6 mmHg, respectively. Regional HSP70 and myocardial blood flow (RMBF) were measured using an HSP70-enzyme-linked immunosorbent assay and the tracer microsphere technique, respectively, in samples of 250 mg wet mass. In the control group the mean RMBF was 1.06+/-0.59 ml.min-1.g-1 and the local HSP70 concentration was 7.08+/-1.03 microg/mg cytosolic protein. Myocardial HSP70 showed a blood flow-independent regional biological heterogeneity, equivalent to a coefficient of variation of 0.31. Local HSP70 concentrations did not differ (P>0.05) between control low and high flow samples, 6.16+/-1.0 vs 6.08+/-0.75 microg/mg cytosolic protein, respectively. However, after 60 min of coronary artery occlusion the local HSP70 concentration increased from 7.08 +/-1.03 to 13.43+/-3.19 microg/mg cytosolic protein (P<0. 001). There was a significant inverse relationship between the percent reduction of local blood flow and HSP70 (r=-0.56, P<0.001). From these results it is concluded that: (1) low flow samples under control physiological conditions are unlikely to be in a state of hibernation or stunning since their HSP70 concentration is normal and (2) the increase in the local HSP70 concentration during myocardial ischaemia reflects the degree of impairment of O2 delivery.

Animals↗
PubMed1998

Patient-controlled versus staff-controlled analgesia with pethidine after allogeneic bone marrow transplantation.

Patients treated by allogeneic bone marrow transplantation (aBMT) suffer prolonged oropharyngeal mucositis pain. The aim of this study was to prospectively compare patient-controlled analgesia (PCA) with an established regimen of staff-controlled analgesia using pethidine (meperidine). Twenty patients undergoing aBMT for haematologic neoplasias or malignant lymphomas randomly received pethidine intravenously either continuously plus supplemental bolus doses on request through the transplant unit staff or by PCA. Pain intensity was assessed by patient self report using a visual analogue scale (VAS) and daily pethidine intake was documented. In addition, the pethidine consumption of 20 aBMT-patients receiving staff-controlled analgesia prior to initiation of the study, but not reporting pain, was compared retrospectively with that of patients receiving the same analgesia regimen under study conditions. PCA significantly diminished both pethidine consumption and pain intensity compared with staff-controlled analgesia. The maximum pethidine intake was 440.1 +/- 111.8 mg/24 h in the patient-controlled and 640.9 +/- 128.9 mg/24 h in the staff-controlled analgesia group (mean +/- 95% CI). Mean pain scores remained under 50% but reached 70% in the staff-controlled analgesia group. Pethidine dosage by staff-controlled analgesia increased under study conditions, suggesting that mere pain-assessment and a 'competing' analgesic method motivated the BMT-unit staff to administer higher pethidine doses. This observation is discussed as a possible Hawthorne effect. Previous studies using morphine demonstrated that PCA diminishes opioid requirement compared to continuous or staff-controlled application in bone marrow recipients. In contrast to these studies, PCA additionally improved pain relief in the present investigation.

Adult↗
PubMed1997

Determinants of the S-adenosylhomocysteine (SAH) technique for the local assessment of cardiac free cytosolic adenosine.

The S-adenosylhomocysteine (SAH) technique allows the estimation of the free cytosolic adenosine concentration using the kinetic properties of the enzyme SAH-hydrolase (adenosine+homocysteine reversible SAH+H2O). Besides the cytosolic adenosine concentration, the local SAH signal may also depend on the local homocysteine availability, the continuous production of SAH from S-adenosylmethionine (SAM-->SAH+CH3) and the activity of the enzyme SAH-hydrolase. These variables were studied with high spatial resolution (sample dry mass 25 mg) in left ventricular myocardium from 26 anesthetized open-chest dogs in which heart rate averaged 86 +/- 14 beats/min and mean aortic pressure 96 +/- 17 mmHg. Homocysteine infusion (48 mg/kg i.v.) increased the normal plasma homocysteine concentration from 5.0 +/- 0.8 to 586 +/- 40 microM after 30 min when the average tissue concentration was 94% of the plasma concentration and similar in low and high flow areas (flow range 0.04 to 1.91 ml/min/g). Local SAH content was 1.18 +/- 0.48 nmol/g under control conditions and increased to 4.33 +/- 0.59 nmol/g within 60 min following competitive blockage of the SAH-hydrolase by adenosine dialdehyde (10 mumol/kg i.v.). This increase of the SAH content was slightly more in high than in low-flow areas (P < 0.01). Regional SAH-hydrolase activity (9.0 +/- 0.5 nmol/min/g) was comparable in high and low flow areas. All three variables exhibited an observed variability which was larger than the methodical variability suggesting significant spatial heterogeneity in the myocardium. A regrouping analysis indicated that between four and five samples taken from distant sites should be averaged to obtain a robust estimate of the above metabolic parameters. Reconciling the measurements with a mathematical model of cardiac adenosine metabolism and fitting of the measured SAH tissue levels gave an estimate of 72 pmol/min/g for the mean transmethylation rate. Estimates of the cytosolic adenosine concentration of cardiomyocytes and endothelial cells under control physiological conditions were 24 and 7 microM, respectively. Thus, the present measurements provide a basis for the quantitative assessment of the local cytosolic adenosine concentration in relation to blood flow.

Adenosine↗
PubMed1997

Minimal effects of nitric oxide on spatial blood flow heterogeneity of the dog heart.

Eleven Beagle dogs were studied to elucidate the possible role of L-arginine-derived nitric oxide on local blood flow distribution in left and right ventricular myocardium. Local blood flow was determined in 256 samples from the left and 64 samples from the right ventricle per heart using the tracer microsphere technique (mean sample mass 319 +/- 131 mg). Nitric oxide production was effectively inhibited by intravenous infusion of 20 mg/kg nitro-L-arginine methylester (L-NAME) as evidenced by a shift of the dose/response curve for the effect of intracoronary administration of bradykinin (0.004-4.0 nmol/min) on coronary blood flow. L-NAME enhanced left and right ventricular systolic pressures from 132 +/- 18 to 155 +/- 15 mm Hg and from 26 +/- 3 to 29 +/- 3 mm Hg respectively (both P = 0.043). Mean left ventricular blood flow was 1.14 +/- 0.38 before and 0.99 +/- 0.28 ml min-1 g-1 after L-NAME (P = 0.068), while right ventricular blood flow fell from 0.72 +/- 0.28 to 0.53 +/- 0.20 ml min-1 g-1 (P = 0.043). Coronary conductance of left and right ventricular myocardium fell by 31 and 43% respectively (both P = 0.043). The coefficient of variation of left ventricular blood flow was 0.26 +/- 0.07 before and 0.29 +/- 0.07 after L-NAME (P = 0.068), that of right ventricular blood flow was 0.27 before and after L-NAME. Skewness (0.51) and kurtosis (4.23) of left ventricular blood flow distribution were unchanged after L-NAME, while in the right ventricle skewness decreased from 0.54 to 0.09 (P = 0.043) and kurtosis (3.68) tended to decrease after L-NAME (P = 0.080). The fractal dimension (D = 1.20-1.27) and the corresponding nearest-neighbor correlation coefficient (rn = 0.37-0.53) of left and right ventricular myocardium remained unchanged after infusion of L-NAME. From these results it is concluded that firstly, local nitric oxide release does not explain the higher perfusion of physiological high flow samples and secondly, that spatial myocardial blood flow coordination is not dependent on nitric oxide.

Animals↗
PubMed1997

[The AIDS patient in anesthesia].

Treatment of a patient with Acquired Immune Deficiency Syndrome (AIDS) is very challenging, and makes great demands on the anaesthesiologist. Any of an AIDS patient's vital organ systems may be compromised, either by the human immunodeficiency virus (HIV) itself, opportunistic infections, by tumours, or as a result of AIDS-related drug therapies. Infections of the lungs (e.g., Pneumocystis carinii pneumonia) are prevalent, and cardiac impairment can be found in as many as 50% of AIDS patients. In addition, disorders of the central and peripheral nervous system and water and electrolyte imbalances are often seen. Perioperatively, the AIDS patient is especially prone to infections as a result of a compromised immune system. The choice of anaesthetic procedure for the AIDS patient-aside from the type of operation-depends on the severity of the illness and progression of organ impairment. All anaesthesia personnel must be careful to avoid infection, as they frequently come in contact with the blood or body fluids of their patients. However, the risk of being infected by an AIDS patient is very low, provided hygiene regulations are followed strictly. The rate of seroconversion after accidental needle-stick injury is below 1%. If exposure does occur, regular serologic controls should be continued for one year. Prophylactic treatment with azidothymidine after exposition to HIV is recommended.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Spatial heterogeneity of blood flow in the dog heart. II. Temporal stability in response to adrenergic stimulation.

The effects of adrenergic stimulation on local myocardial blood flow in the left ventricle were studied in 13 anaesthetized Beagle dogs using the tracer microsphere technique. Adrenergic stimulation was induced by intravenous infusion of orciprenaline (1-2 microg kg-1 min-1) over 15 min or by electrical stimulation of the left ansa subclavia (10 Hz, 1 ms, 4-8 V) over 5 min. Local myocardial blood flow was analysed in 256 samples with an average (+/-SD) mass of 318+/-49 mg from the left ventricular myocardium using a standardized dissection procedure. Orciprenaline increased the average myocardial blood flow from 0.85+/-0.18 to 1.73+/-0.27 ml min-1 g-1, while oxygen consumption and the pressure-rate product increased by 129 and 119% respectively. The coefficients of variation of local myocardial blood flow, a measure of spatial blood flow heterogeneity, were 0.21 and 0.18 under control and orciprenaline respectively. Except for a slight transmural gradient (endomyocardium/epimyocardium flow ratio 1.19) myocardial blood flow did not exhibit significant spatial gradients. Stimulation with orciprenaline increased the average blood flow in all regions of the left ventricle by comparable extents. However, local blood flow during orciprenaline was significantly lower in samples from regions which had a lower blood flow under resting control conditions. A significant positive relationship was obtained between local myocardial blood flow under resting conditions and orciprenaline (r=0.45+/-0.18). Moreover, after recovery from orciprenaline stimulation (i.e. 40-112 min after the end of orciprenaline infusion) local myocardial blood flow exhibited a high degree of correlation with local flow before orciprenaline (r=0.71+/-0.08). Comparable results were obtained with electrical stimulation of the left ansa subclavia. For the comparison stimulation vs. control, the correlation coefficient of local blood flow was 0.52+/-0.04 and for recovery vs. control 0.77+/-0.06. From these results it is concluded firstly that local myocardial blood flow under resting conditions is an important determinant of local flow during adrenergic stimulation. Secondly, the anatomical region does not have any predictive value for the blood flow change during adrenergic stimulation and finally, the close relationship between local blood flow before and after cardiac stimulation indicates that the spatial blood flow heterogeneity is temporally stable over hours.

Adrenergic Agonists↗
PubMed1996

[Family practice management of risk patients with reference to preclinical emergency medicine].

Chances of surviving myocardial infarction or cardiocirculatory arrest depend on an early and appropriate emergency call as well as on bystander CPR. This study uses a questionnaire to assess to what extent these factors guide the private practitioners caring for high-risk cardiac patients. Almost all physicians responding (44%) treat such patients. More than 70% try to include the patients' relatives in a medical briefing. Recognition of early warning signs is discussed with 80% of the patients and 70% of relatives. How to identify acute life-threatening conditions is discussed with 60% of patients and relatives. In case of sudden chest pain and dyspnoea, physicians commonly advise calling the family doctor, a hospital or a regional physician on call. Calling 112, the emergency physician/rescue service, is rarely recommended. Initiating CPR is recommended for an emergency by 30% of the physicians, whereas 20% encourage relatives of patients at risk to take a CPR course. CPR instruction is judged to be generally useful by 50% of physicians, of limited use by 40% and of no use by 10%. When asked why they do not encourage CPR, 15% of physicians said they have no time, 25% cited the inefficiency of the courses, 40% said CPR is psychologically too stressful for laypersons, and 50% felt it was physically too stressful. This study points out the necessity of additional, appropriate instruction of laymen regarding cardiac emergencies.

Cardiopulmonary Resuscitation↗
PubMed1995

Observation of reorientationally hindered water in biological tissue using triple quantum filtered 17O-NMR.

Water dynamics in aqueous biopolymer solutions often display a two-phase character, resembling water-water and water-protein interactions. Rotationally hindered water molecules in crowded protein environments display triple exponential magnetic relaxation out of the extreme narrowing limit. Because water-protein interactions retard the water dynamics, H2O(17) magnetization passes through a NMR multiple quantum coherence filter, allowing the visualization of reorientationally hindered water without the disturbing resonance of the bulk. In vitro experiments performed on selected biological materials (lens, vitreous body and serum albumin solutions) clearly demonstrate the potential of this technique.

Animals↗
PubMed1995

Endotoxin-induced contractile dysfunction in guinea pig hearts is not mediated by nitric oxide.

The decreased contraction amplitude of isolated cardiac myocytes from guinea pigs exposed to lipopolysaccharide (LPS) was reported to be partially reversed by nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) [Brady, et al., Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1963-H1966, 1992]. We have tested the potential involvement of NO formation in LPS-induced cardiac depression in the intact heart. Isolated perfused hearts of LPS-treated guinea pigs (4 mg/kg 4 h before organ removal) displayed a greatly decreased left ventricular pressure (LVP) when compared with untreated controls (48 +/- 11 vs. 93 +/- 18 mmHg, n = 6 hearts each), whereas heart rate and coronary flow were similar. Perfusion of LPS-treated hearts with L-NMMA or L-NAME (100 microM each) at constant flow did not increase LVP (50 +/- 14 and 44 +/- 11, respectively, vs. 52 +/- 14 mmHg). However, coronary resistance increased significantly. There was no difference between LPS-treated and control hearts in venous adenosine release (104 +/- 58 vs. 133 +/- 86 pmol.min-1.g-1). Measurement of the activities of the induced (iNOS) and constitutive forms of NOS revealed that there was no difference in total NOS activity (237 +/- 82 vs. 181 +/- 97 fmol.min-1.mg protein-1. There was no measurable induction of iNOS in the LPS-treated hearts either. Finally, cardiac energy status was studied by 31P nuclear magnetic resonance spectroscopy. There was no difference between LPS-treated and control hearts in myocardial ATP, creatine phosphate, pH, and free ADP (59 +/- 20 vs. 50 +/- 27 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1995

[Latex allergy].

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Dermatitis, Allergic Contact↗