Robert Gasser

Changes in thyroid hormone parameters after acute myocardial infarction

Abnormalities in circulating thyroid hormone levels are very common in systemic nonthyroidal illnesses, such as acute myocardial infarction. In this study, thyroid parameters were determined in a series of 16 consecutive infarction patients treated by thrombolysis. Blood samples were taken before therapy as well as 2, 4, 6, 8, 12 and 72 h following admission. Total and free serum thyroxin and triiodothyronine decreased and reverse T3 increased significantly showing no major variations up to 72 h, whereas thyroid-stimulating hormone values remained almost unchanged during the observation period. Subjects with CK-MB levels of more than 150 ng/ml (n = 10) revealed similar changes in thyroid parameters in comparison to those with lower values (n = 6; NS). Thus, although hormone modifications very often occur following acute infarction, thyroid status may not serve as a marker for the extent of left ventricular dysfunction in the early phase of myocardial infarction.

Glucose-transporter-mediated positive inotropic effects in human myocardium of diabetic and nondiabetic patients.

Insulin causes inotropic effects via Ca(2+)-dependent and Ca(2+)-independent pathways. The latter one is potentially glucose dependent. We examined inotropic responses and signal transduction of insulin in human atrial myocardium of diabetic and nondiabetic patients to test for the role of glucose transporters. Experiments were performed in isolated atrial myocardium of 88 patients undergoing cardiac surgery and 28 ventricular muscle samples of explanted hearts. Influence of insulin (0.02 micromol/L) on isometric twitch force was examined with and without blocking glucose transporter (GLUT) 4 translocation (latrunculin), sodium-coupled glucose transporter (SGLT) 1 (phlorizin, T-1095A), or PI3-kinase (wortmannin). Experiments were performed in Tyrode solution containing glucose or pyruvate as energetic substrate. Messenger RNA expression of glucose transporters (GLUT1, GLUT4, SGLT1, SGLT2) was analyzed in atrial and ventricular myocardium of both diabetic and nondiabetic patients. Developed force increases after insulin (to 117.8% +/- 2.4% and 115.8% +/- 1.9%) in trabeculae from patients with and without diabetes. Inotropic effect was reduced after displacing glucose with pyruvate as well as after PI3-kinase inhibition (to 103% +/- 2%) or inhibition of glucose transporters GLUT4 (to 105% +/- 2%) and SGLT1 (phlorizin to 106% +/- 2%, T-1095A to 105% +/- 2%), without differences between the 2 groups. In glucose-free pyruvate-containing solution, only inhibition of PI3-kinase but not blocking glucose transporters resulted in further inhibitory effects. Messenger RNA expression did not show significant differences between patients with or without diabetes. Insulin exerts positive inotropic effects in human atrial myocardium. These effects are mediated via a PI3-kinase-sensitive and a glucose-transport-sensitive pathway. Differences in functional effects or messenger RNA expression of glucose transporters were not detectable between patients with and without diabetes.

G-455A polymorphism of the fibrinogen beta gene and deep vein thrombosis.

Background Elevated fibrinogen levels have been linked to increased risk for deep venous thrombosis, although it is not clear whether fibrinogen is causal or rather a marker for the presence of other risk factors. A common G/A polymorphism in the gene for the fibrinogen beta‐chain (FGB G‐455A) is associated with elevated fibrinogen levels. The present study was designed to analyze the role of this genetic marker for deep venous thrombosis.

Functional effects of glucose transporters in human ventricular myocardium

Insulin‐dependent positive inotropic effects (PIE) are partially Ca2+ independent. This mechanism is potentially glucose dependent. In contrast to most animal species, human myocardium expresses high levels of sodium‐glucose‐transporter‐1 (SGLT‐1) mRNA besides the common glucose‐transporters‐1 and ‐4 (GLUT1, GLUT4).

The Interdependence of Hypertension, Calcium Overload, and Coronary Spasm in the Development of Myocardial Infarction

It is a well-known fact that sys temic hypertension is one of the ma jor risk factors for myocardial in farction (MI). Extensive studies on hypertensive rats revealed that cal cium is excessively elevated in the myocytes, as well as in the coronary artery wall of these animals, which results in a higher resting tension and a stronger contractile response of those muscle strips. Over many years coronary spasm has been claimed by various authors to be greatly involved in the patho physiology of the early phase of acute MI (AMI). It can be shown that thrombocytes that aggregate at the injured vessel wall next to athero slcerotic plaques release vasocon strictive factors that induce series of severe spasms at the sites with defec tive endothelium that end up in myocardial infarction; the patho physiologic pathway is called the thromboischemic reentry mechan ism. This local contractile response may be enhanced in the presence of systemic hypertension since intracel lular calcium is elevated in the coro nary smooth muscle. On the other hand, it has been shown that heart muscle fibers un dergo severe alterations finally re sulting in necrotization, as soon as free calcium ions penetrate exces sively through the sarcolemma mem brane into the myoplasm so that the capacities of the calcium binding or extrusion processes become overpow ered ; this is especially the case during ischemia. Since free intracellular cal cium is already ten times elevated in the myocytes in systemic hyperten sion, the myocardium may be more vulnerable to further calcium over load owing to the ischemia and ne crotization is augmented. The elevation of intracellular Ca of the myocytes of the cardiovascular system in systemic hypertension en hances the pathologic response of the coronary arteries and the myocar dium. This work gives a complete overview of the pathophysiologic principles involved in AMI occurring with systemic hypertension.

Antibiotics and Increased Temperature against Borrelia burgdorferi in Vitro

In 1917, spirochaetal neurosyphilis was treated successfully with malariotherapy in combination with salvarsan or bismuth. Malariotherapy for spirochaetal Lyme disease has been discussed, but the mechanism of an antispirochaetal effect remains unclear. We cultured Borrelia burgdorferi at different temperatures, alone and in combination with antibiotics. Our data demonstrate that growth of the strains PKo and ATCC 35210 (B31) was impaired at temperatures of 37 degrees C and inhibited at 39 degrees C and 40 degrees C, respectively. Strain ATCC 35211, however, grew well up to 39 degrees C but did not multiply at 40 degrees C. A bactericidal effect was seen at 41 degrees C for the strains B31 and PKo and at 42 degrees C for all strains. The susceptibility of all strains to penicillin and ceftriaxone was increased up to 16-fold by an elevation of temperature from 36 degrees C to 38 degrees C. These in vitro data suggest that elevated body temperature may be beneficial during antimicrobial treatment of Lyme disease. This may be particularly important in tissues where high concentrations of antibiotics are difficult to achieve.

The angiotensin-converting-enzyme insertion/deletion polymorphism is not related to venous thrombosis

The insertion/deletion (I/D) polymorphism of the gene for angiotensin-converting-enzyme (ACE) is associated with ACE plasma levels and activity. Conflicting results have been reported about the relevance of this polymorphism for venous thrombosis. The aim of the present study was to analyze the role of this polymorphism for deep venous thrombosis. The study was designed as a case-control study, including 330 patients with documented deep venous thrombosis and 354 controls. ACE genotype was determined by size-analysis of polymerase chain reaction products. Results showed that, ACE genotype frequencies were similar between patients (II: 24.8%; ID: 43.3%; DD: 31.8%) and controls (II: 22.9%; ID: 50.6%; DD: 26.6%, P = 0.15). The adjusted odds ratio of carriers of the DD geno-type for venous thrombosis was 1.24 (95% confidence interval 0.90-1.80). The polymorphism was furthermore not associated with age at first thromboembolic event or the occurrence of pulmonary embolism. From these results, we can conclude that the ACE I/D polymorphism is not a significant risk factor for deep venous thrombosis.

Vasodilative Response to Hypoxia and Simulated Ischemia Is Mediated by ATP-Sensitive K + Channels in Guinea Pig Thoracic Aorta

Local vasodilation in response to hypoxia or ischemia improves perfusion and O2 supply of the affected tissue. This local vasodilation thus constitutes the most important mechanism in the prevention of ischemic cell injury. The regula tion of vascular tone has mainly been attributed to changes of cytoplasmatic Ca2+ ((Ca2+)i) concentrations in vascular smooth muscle cells. The mechanism underlying these changes has not, however, been elucidated so far. Using aortic strips of guinea pigs (transversally cut in spirals; normal Tyrode, in mM: NaCl 150, KCI 4.5, MgCl2 2, CaCl2 2.5, glucose 10; buffered with 10 mM HEPES at pH 7.4; equilibrated with 100% O2 at 31°C) the authors could show that metabolic blockade (glucose replaced by 10 mM 2-deoyglucose (DOG) led to a relaxation of the preparation. Thus, in four experiments, resting tension decreased from 0.75 g by 27% ± 12% within two hours (% of maximal contractile force developed by each prepa ration when depolarized with 43 mM KCI and 101.5 mM NaCl). When the same experiment was carried out in the presence of 1 mM tolbutamide (a known blocker of ATP-dependent K+ channels) in vascular smooth muscle no such re laxation could be seen (n = 4). Furthermore, in the same type of preparation, similar results have been obtained upon hypoxic relaxation (100% O2 replaced by 100% N2), where 1 mM tolbutamide also prevented vasodilation. Thus, hypoxic/ischemic vasodilation in response to glycolytic inhibition (DOG) and hypoxia (N2) is based upon the opening of K+ ATP channels and hence can be prevented by sulfonylureas (the opening of K+ ATP channels would lead to hyperpolarization (increased K+ conductance, Goldmann equation), thus di minishing the open probability of voltage-gated Ca2+ channels with subsequent vasodilation). This inhibition by sulfonylureas of vasodilative response to ischemia may also constitute the so far unknown cause of the increased cardiovascular mortal ity seen under sulfonylurea treatment.

Ophthalmic manifestations in Lyme borreliosis. A review.

Lyme borreliosis is an emerging tickborne spirochetal infection characterized by a broad variety of symptoms, ranging from neurologic disorders and different skin manifestations to cardiac symptoms. Many ocular and neuro-ophthalmic symptoms have recently been attributed to Lyme disease. Especially in endemic areas ophthalmologists need to be aware of Borrelia burgdorferi as a possible causal agent. The aim of this paper is to present a short review of the literature of ophthalmic disorders resulting from Borrelia burgdorferi infections.

Reversal of Borrelia burgdorferi Associated Dilated Cardiomyopathy by Antibiotic Treatment

SummaryIt is suggested thatBorrelia burgdorferi infection could be associated with dilated cardiomyopathy (IDC). Stanek et al. were able to cultivateBorrelia burgdorferi from myocardial biopsy tissue of a patient with longstanding dilated cardiomyopathy. Here we present a study in which we examined the effect of standard antibiotic treatment on the left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy associated withBorrelia burgdorferi infection. In this study we assessed the serum (IgG, IgM Elisa) and history of 46 IDC patients with specific regard toBorrelia burgdorferi infection (mean LVEF 30.4±1.3%, measured by cardiac catheterization and echocardiography with the length-area-volume method). All 46 patients received standard treatment for dilated cardiomyopathy: ACE inhibitors, digitalis, and diuretics. Eleven (24%) patients showed positive serology and a history ofBorrelia burgdorferi infection; nine of these also had a typical history of tick bite and erythema chronicum migrans (ECM) and/or other organ involvement, and two had no recollection of tick bite or ECM but showed otherBorrelia burgdorferi-associated disorders (neuropathy, oligoarthritis). These 11 patients withBorrelia burgdorferi infection received standard antibiotic treatment with intravenous ceftriaxone 2 g bid for 14 days. Six (55%) recovered completely and showed a normal LVEF after 6 months, three (27%) improved their LVEF, and two (18%) did not improve at all. This amounts tonine (82%) patients with recovery/improvement in the Borrelia burgdorferi group. The 35 patients who did not show positive serology or a history ofBorrelia burgdorferi infection did not receive antibiotic treatment. In thisgroup without Borrelia burgdorferi infection 12 (26%), showed recovery/improvement following the standard treatment of dilated cardiomyopathy (see earlier). Our results indicate thatBorrelia burgdorferi infection could play a decisive role in the development of dilated cardiomyopathy, especially in a geographical region such as Graz, whereBorrelia burgdorferi is endemic. While we are aware of the small number ofBorrelia burgdorferi patients in this study, we nevertheless conclude that in a remarkable number of patients with signs ofBorrelia burgdorferi infection, dilated cardiomyopathy could be reversed and LVEF improved.