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Biomedical subjects

M Kelm

Publications and source records attributed to M Kelm.

At least 19 recordsLinked to original sources

[Duplex ultrasound determination of shunt volume in iatrogenic arteriovenous fistulas after heart catheterization].

AIM: To determine the shunt volume of iatrogenic arteriovenous fistula (AVF) following arterial puncture of the groin and to evaluate its impact on natural history and clinical outcome. METHOD: Over a period of 12 months, 22 patients (p) with a newly acquired AVF were followed up. The arteriovenous shunt volume was determined by means of colored duplex- and doppler sonography immediately after diagnosis of AVF. RESULTS: Spontaneous closure of AVF was seen in 10 p (46%) during follow-up examination, whereas 12 p (54%) showed a persistence of their AVF. The median (I50) shunt volume of closed AVF was 310 (250-350) ml/min and 350 (160-510) ml/min for persistent fistulae (p = ns). A shunt volume of > or = 400 ml/min was determined as a significant (p < or = 0.05) cut-off point for prolonged persistence of AVF. CONCLUSION: Because spontaneous closure of AVF was 46% in the course of the first year, conservative management with regular duplex control seems to be justified at least for this duration. Patients with a shunt volume of > or = 400 ml/min have an increased risk of prolonged AVF persistence and therefore should be included in long-term follow-up with special attention to development of hemodynamic relevance.

Arteriovenous Fistula↗

[Lipoid pneumonia following attempted suicide by intravenous injection of lamp oil].

BACKGROUND: Pneumonic complications after intoxication with mineral oils have been described before in the contents of accidental aspiration and oral ingestion. However, intoxication following an intravenous injection leading to a lipoid pneumonia after an attempted suicide is a rare finding. CASE REPORT: A case report is presented of an attempted suicide by intravenously self-injection of 20 ml lamp oil (liquid paraffin). Immediately after injection the patient suffered from dry coughing which changed in the course of the next hours into a productive cough with white thick mucous sputum accompanied by hemoptysis. Additionally, he developed a mild disseminated intravascular coagulation with a fall of thrombocytes, an INR of 1.6 and a rise of D-dimeres. Under a therapy with hydrocortisone, ascorbic acid, ambroxol, acetylcysteine, heparin, antibiotics and oxygen, the patient improved without the need of mechanical ventilation. Initially seen signs of right heart dilatation diminished 3 days after onset of therapy. Apart from pulmonal manifestation no relevant organ damage was observed. The patient was discharged from the intensive care unit 9 days after intoxication and was submitted to psychiatric therapy. CONCLUSION: Lipoid pneumonia caused by intoxication with a mineral oil is a severe disease, whereas in the presented case a relative bland course of the disease has been seen. The employed therapy in this patient might be encouraging for a comparable treatment of pneumological complications resulting from similar clinical pictures.

Adult↗

Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action.

The plasma level of NO(x), i.e., the sum of NO(2)- and NO(3)-, is frequently used to assess NO bioavailability in vivo. However, little is known about the kinetics of NO conversion to these metabolites under physiological conditions. Moreover, plasma nitrite recently has been proposed to represent a delivery source for intravascular NO. We therefore sought to investigate in humans whether changes in NO(x) concentration are a reliable marker for endothelial NO production and whether physiological concentrations of nitrite are vasoactive. NO(2)- and NO(3)- concentrations were measured in blood sampled from the antecubital vein and brachial artery of 24 healthy volunteers. No significant arterial-venous gradient was observed for either NO(2)- or NO(3)-. Endothelial NO synthase (eNOS) stimulation with acetylcholine (1-10 microg/min) dose-dependently augmented venous NO(2)- levels by maximally 71%. This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO(2)-. Intraarterial infusion of NO(2)- had no effect on FBF. NOS inhibition (N(G)-monomethyl-l-arginine; 4-12 micromol/min) dose-dependently reduced basal NO(2)- and FBF and blunted acetylcholine-induced vasodilation and NO release by more than 80% and 90%, respectively. In contrast, venous NO(3)- and total NO(x) remained unchanged as did systemic arterial NO(2)- and NO(3)- levels during all these interventions. FBF and NO release showed a positive association (r = 0.85; P < 0.001). These results contradict the current paradigm that plasma NO(3)- and/or total NO(x) are generally useful markers of endogenous NO production and demonstrate that only NO(2)- reflects acute changes in regional eNOS activity. Our results further demonstrate that physiological levels of nitrite are vasodilator-inactive.

Acetylcholine↗

The nitric oxide-induced reduction in cardiac energy supply is not due to inhibition of creatine kinase.

OBJECTIVES: While nitric oxide (NO) is a potent vasodilator already in the nM range, a cGMP-independent negative inotropic effect is observed at higher concentrations. Since inhibition of creatine kinase (CK) by NO-induced nitrosylation has been proposed as a possible mechanism of action, we measured the flux through CK in the intact heart. METHODS: In saline perfused, paced guinea pig hearts 31P NMR spectroscopy was employed to directly assess the cardiac energy status, i.e. free energy of ATP hydrolysis (DeltaG(ATP)) and flux through CK using magnetization transfer in absence and presence of NO. RESULTS: NO (50 microM) doubled coronary flow and induced a rapid drop in left ventricular developed pressure (39+/-10 vs. 81+/-10 mmHg) and MVO(2) (1.3+/-0.8 vs. 3.7+/-0.5 micromol/min/g) (n=7). This effect was associated with an immediate decrease in phosphocreatine (PCr) (-69%) and DeltaG(ATP). During the subsequent 35 min of NO infusion cardiac function and MVO(2) remained depressed, while PCr partially recovered. NO had no effect on the unidirectional forward flux through CK (98 +/- 21 vs. 99 +/- 20 micromol/min/g, n=7) which was 5- to 10-fold greater than the rate of ATP turnover. Upon cessation of NO infusion both cardiac function and PCr rapidly returned to baseline values. The NO-induced fall in the myocardial energy status was associated with an increase in mitochondrial NADH (n=7) as assessed by surface fluorescence. The observed change in fluorescence was similar to that observed with short term ischemia. CONCLUSION: The NO-mediated depression of myocardial function, MVO(2) and energy status is not mediated by changes in CK flux. Most likely a partial blockade of mitochondrial oxidative phosphorylation at the level of cytochrome c oxidase is responsible for this effect.

Animals↗

[Interaction of the coronary macro- and microcirculation].

In the following the impact of epicardial vessels on flow regulation in downstream resistive arteries and, vice versa, the potential influence of coronary microvascular disease on upstream conduit arteries will be reviewed. There is ample evidence that coronary artery disease of epicardial vessels leads to microvascular dysfunction not only due to a flow limiting stenoses with an altered regulation of vessel tone in the intra- and poststenotic segments, but also via distal microembolization of atherosclerotic material derived from upstream plaques. On the other hand, patients with hypertensive microvascular disease frequently reveal a disturbed endothelium-dependent and -independent regulation of epicardial vessel tone, although angiographic appearance is regular. Most strikingly, it could be demonstrated that in these patients with microvascular disease the incidence of coronary artery disease of epicardial vessels is increased several-fold as compared to age-matched populations. These findings suggest that hypertensive microvascular disease independent from the direct effect of hypertension on epicardial vessel affects upstream conduit arteries. Therefore a thorough and careful follow up of hypertensive patients with initially normal coronary arteriograms but preexistent microvascular disease appears advisable.

Animals↗

[Determination of right ventricular ejection fraction by thermodilution catheter technique during exercise: a comparison with radionuclide ventriculography].

Since the development of a Swan-Ganz Thermodilution Ejection Fraction Catheter, several studies have been published which compare this technique for obtaining right ventricular ejection fraction (RVEFTD) with alternative methods. However, the reliability of RVEFTD measurements under exercise conditions remains undetermined. Therefore, the aim of the present study was to evaluate RVEFTD with the Gated Blood Pool method (RVEFGBP) under exercise conditions. Twenty patients with different cardiac diseases (coronary artery disease, valvular incompetence, cardiomyopathy) underwent right heart catheterization, including RVEFTD and simultaneous RVEFGBP determination at rest and during supine bicycle exercise. Cardiac index at rest-/exercise was 2.9 +/- 0.8/5.7 +/- 2.2 l/min/m2, mean pulmonary artery pressure was 15 +/- 5/25 +/- 8 mmHg, RVEFTD was 38 +/- 6/41 +/- 11% and RVEFRNV was 39 +/- 6/43 +/- 8%. Linear regression analysis showed a significant correlation between RVEFTD and RVEFGBP at rest (r = 0.72, p < or = 0.0005) and during exercise (r = 0.72, p < or = 0.0005). It is concluded that the Thermodilution Ejection Fraction Catheter is a useful device for reliable, repetitive and safe RVEF measurements, not only at rest but also under exercise conditions. This is clinically important, because RVEF, as a sensitive parameter of primary or secondary right ventricular dysfunction, can be determined in the course of standard right heart catheterization.

Adult↗

Vineberg graft: flow reserve of bilateral implantation after 27 years.

We report a patient who underwent bilateral internal thoracic artery implantation into the myocardium known as a Vineberg procedure 27 years ago. Coronary angiography and Doppler echocardiography revealed patent grafts with total occlusion of all native coronary arteries. We measured flow velocities at rest and under stress conditions with noninvasive ultrasonic Doppler echocardiography. The flow patterns in both grafts were biphasic as in native coronary arteries. Under stress conditions no increase in flow was detectable as a marker of end-stage coronary artery disease with refractory angina pectoris.

Angina Pectoris↗

Comparative evaluation of thermodilution and gated blood pool method for determination of right ventricular ejection fraction at rest and during exercise.

BACKGROUND: Since the development of a Swan-Ganz thermodilution ejection fraction catheter several studies have been published which compare this technique for obtaining right ventricular ejection fraction (RVEF(TD)) with alternative methods. However, the reliability of RVEF(TD) measurements under exercise conditions remains undetermined. Therefore, the aim of the present study was a comparative evaluation of RVEF(TD) with the established gated blood pool method (RVEF(GBP)) under exercise conditions. METHODS AND RESULTS: Twenty-two patients with different cardiac diseases underwent right heart catheterization, including RVEF(TD) and simultaneous RVEF(GBP) determination at rest and during supine bicycle exercise. Linear regression analysis showed a significant correlation between RVEF(TD) and RVEF(GBP) at rest (r = 0.73, p < or = 0.0005) and during exercise (r = 0.74, p < or = 0.0005). A Wilcoxon analysis showed a high probability of agreement of RVEF(TD) and RVEF(GBP) at rest and exercise (level of significance for error of the 0 hypothesis of 95.9/73.3%). CONCLUSION: The thermodilution ejection fraction catheter provides a useful device for reliable, repetitive and safe RVEF measurements, not only at rest but also under exercise conditions. This seems to be clinically important, because by it means RVEF, as a sensitive parameter of primary or secondary right ventricular dysfunction, can be determined in the course of standard right heart catheterization.

Adult↗

Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin.

Nitric oxide (NO) induces vasodilatatory, antiaggregatory, and antiproliferative effects in vitro. To delineate potential beneficial effects of NO in preventing vascular disease in vivo, we generated transgenic mice overexpressing human erythropoietin. These animals induce polyglobulia known to be associated with a high incidence of vascular disease. Despite hematocrit levels of 80%, adult transgenic mice did not develop hypertension or thromboembolism. Endothelial NO synthase levels, NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels were markedly increased. Administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) led to vasoconstriction of peripheral resistance vessels, hypertension, and death of transgenic mice, whereas wild-type siblings developed hypertension but did not show increased mortality. L-NAME-treated polyglobulic mice revealed acute left ventricular dilatation and vascular engorgement associated with pulmonary congestion and hemorrhage. In conclusion, we here unequivocally demonstrate that endothelial NO maintains normotension, prevents cardiovascular dysfunction, and critically determines survival in vivo under conditions of increased hematocrit.

Animals↗

[Cardiac complications in diabetes mellitus].

Diabetes mellitus as a disease of epidemiological impact leads to diabetic cardiopathy by modulation of myocardial, vascular and metabolic components. This includes the development of a coronary microangiopathy and a decrease of diastolic and systolic function of the left ventricle as well as the development of an autonomic diabetic neuropathy. Patients with diabetes show an increased mortality concerning cardiovascular events. They more often suffer from myocardial infarction as non-diabetics mostly with a more serious course. Moreover, the post-infarction course is affected with a worse prognosis as in non-diabetics. For diagnosis of cardial involvement in diabetes electrocardiographic and echocardiographic procedures are of use. Special tests of the autonomic function complete the diagnostic ensemble. An early therapy with ACE-inhibitors and beta blocking agents as well as a strong diabetes therapy, in particular with insulin, can influence the mortality favorably. Moreover, the diagnosis and therapy of additional cardiovascular risk factors (arterial hypertension, dyslipidemia) are very important, because these are correlated with a for diabetic patients markedly increased risk of mortality. The clinical relevance of the term diabetic cardiopathy is justified by the 6 factors: macroangiopathy, microangiopathy, disturbances of the myocardial metabolism, myocardial fibrosis, autonomic diabetic neuropathy and disturbances of the coagulability. Diagnostic and therapeutic goals are discussed.

Arteriosclerosis↗

Endogenous nitric oxide and myocardial adaptation to ischemia.

Ischemic myocardium does not inevitably undergo necrosis but rather can survive through downregulation of contractile function, ie, "hibernate." To study the role of endogenous NO in this adaptation, 41 enflurane-anesthetized swine were subjected to 90 minutes of moderate left anterior descending coronary artery hypoperfusion and assigned to placebo (P), to 30 mg/kg N(G)-nitro-L-arginine (L-NNA) IV to inhibit NO synthase, or to aortic constriction (AO) to match the increased left ventricular pressure observed with L-NNA. During normoperfusion, a regional myocardial external work index (WI, mm Hg. mm, sonomicrometry and micromanometry) was reduced with L-NNA (from 326+/-27 [SEM] to 250+/-19, P<0.05) but increased with AO (from 321+/-16 to 363+/-19, P<0.05 versus L-NNA). At 10 minutes of ischemia, WI was lower with L-NNA (109+/-10, P<0.05) than P (180+/-22) and AO (170+/-11) and did not change further at 85 minutes of ischemia. Relationships between WI and transmural myocardial blood flow and oxygen consumption were shifted rightward by L-NNA versus P and AO at both 10 and 85 minutes of ischemia. The maximal increment in calcium-activated external work was not different during normoperfusion among groups but was decreased during ischemia with L-NNA. L-NNA transiently increased myocardial contractile calcium sensitivity along with systemic pressure but reduced it during ongoing ischemia. The free-energy change of ATP hydrolysis after an early ischemic decrease recovered toward baseline values in all groups, and necrosis was absent after 2 (triphenyltetrazolium chloride staining) or 8 (histology) hours of reperfusion. Thus, endogenous NO contributes to hibernation by reducing oxygen consumption and preserving calcium sensitivity and contractile function without an energy cost during ischemia.

Analysis of Variance↗

Age-related decline of PCr/ATP-ratio in progressively hypertrophied hearts of spontaneously hypertensive rats.

Although the ultimate cause for the myocardial dysfunction of hypertensive heart disease is still unclear, a crucial role of the myocardial energy metabolism has been suggested. Therefore, the aim of the present study was to investigate whether age-related myocardial dysfunction in hearts of spontaneously hypertensive rats (SHR) is associated with an impaired myocardial energy metabolism. Isolated hearts of SHR and Wistar Kyoto rats (WKY) aged about 40, 60, and 80 weeks, respectively (each n = 4-5), were perfused according to the working heart technique. Cardiac work and coronary flow were monitored online. Myocardial energy metabolism was evaluated by calculating the ratio of phosphocreatine (PCr) and adenosine triphosphate (ATP) which were measured by nuclear magnetic resonance (31P-NMR) spectroscopy. All hearts were subjected to work for 30min at baseline conditions (low afterload), followed by another 30min under a moderate pressure load (high afterload). Each SHR group showed a higher heart weight/body weight ratio than the age-matched WKY controls. The SHR showed a progressive age-dependent reduction of cardiac work (40 weeks = 5.1+/-0.3, 60 weeks = 4.0+/-0.3, 80 weeks = 3.8+/-0.2 (mW/g) at baseline conditions) and PCr/ATP-ratio (40 weeks = 1.82+/-0.06, 60 weeks = 1.69+/-0.05, 80 weeks = 1.59+/-0.09 (PCr/ATP) at baseline conditions). Similar results were found for hearts of SHR at high afterload. In WKY no significant decline in cardiac work or PCr/ATP-ratio was found under either low or under high afterload. The cardiac work capacity of hearts of SHR progressively decreases with increasing age and left ventricular hypertrophy. This myocardial dysfunction is closely associated with an impaired PCr/ATP-ratio, suggesting a decreased energy reserve.

Adenosine Triphosphate↗

Automated ultrasonic measurement of human arteries for the determination of endothelial function.

AIM: Brachial artery ultrasonography is used to measure flow-mediated dilatation (FMD) as a marker of endothelial function in patients at risk for atherosclerosis. Major disadvantages are the time-consuming manual readings and the high within- and between-observer variability. The authors hypothesize that the ultrasound-based determination of endothelial function can be simplified and refined by an automated analysis system. METHODS AND RESULTS: FMD was quantified by a 7.5 MHz linear transducer following 5 minutes of ischemia of the proximal forearm in 8 healthy volunteers on two occasions. Brachial artery diameter was comparatively assessed 1. manually from the video signal and 2. by a PC-based analyzing system. For the manual readings the mean differences for the FMD were 2.5 +/- 2.3% between-reader, 2.0 +/- 0.9% within-reader and 2.1 +/- 1.5% for scans on different days in contrast to 0.8 +/- 0.4 (between-reader), 0.8 +/- 0.6 (within-reader) and 1.3 +/- 0.9% (day-to-day) for the computerized system. The coefficient of variability for the measurement of arterial diameter was 1.34% for manual readings and 0.78% for the automated analysis system. The mean time for manual readings from S-VHS tapes was 35 minutes in contrast to 9 minutes for the PC-based analysis system. CONCLUSIONS: The new automated analysis system for the boundary detection of the vascular wall reduces the variability and greatly increases the speed of the measurements to determine endothelial function. In future, these advantages will help to screen larger numbers of individuals for endothelial dysfunction, particularly for follow-up and intervention trials, and to reduce the variability between different laboratories.

Adult↗