Should Radiofrequency Therapy Be Performed in Every Symptomatic Patient with Supraventricular Tachycardia? (Pro Drug Position)

The indication for treatment of paroxysmal supraventricular tachycardia depends on the frequency and severity of the tachycardia attacks. If the tachycardia attacks are mildly symptomatic and occur only once or twice a year, there is no indication for either continuous drug therapy or radiofrequency oblation. The only therapeutic measure required is termination of each acute event. If symptoms occur frequently, long-term antiarrhythmic drug therapy is then indicated and will be effective for chronic prophylaxis in most individuals with a low risk of proarrhythmic events. Only in patients with severe or life-threatening symptoms or cases refractory to drug therapy would radiofrequency ablation possibly be justified.     

EFFECTS OF STABILIZERS IN PREPARATIONS OF HUMAN SERUM ALBUMIN ON THE SERUM BILIRUBIN IN GUNN RATS

ABSTRACT. Commercially available preparations of human serum albumin (HSA) containing stabilizers (i.e. 16 mmol/I Na caprylate plus 16 mmol/I Na N-acetyl- dl -tryptophan) were injected either s.c., i.p. or i.v. into homozygous infant Gunn rats. 30 min and 3 hours after s.c. injection, a serum bilirubin decline which surpassed dilution by the injected volume could be ascertained. It was mainly caused by N-acetyl- dl -tryptophan since s.c. injections of appropriate amounts of this substance alone or a mixture of both components of the stabilizer without HSA brought about similar results. HSA without these stabilizers had not such an effect. It is postulated that under these conditions Na N-acetyl- dl -tryptophanate displaced bilirubin from albumin bonds. It became obvious that after s.c. injection equilibration of HSA between skin and plasma was delayed, whereas Na N-acetyl- dl -tryptophan was rapidly transported to the blood. As for Na caprylate, a displacing effect of short duration could not be excluded by the experimental arrangement used, since the metabolism of the substance in the rat is very fast. When HSA and the stabilizers entered the plasma simultaneously (i.v. injection) no effect on serum bilirubin concentration could be proved 30 min and 3 hours later. All the bilirubin and the Na N-acetyl- dl -tryptophan present in the plasma at that time can be bound to the large amount of albumin which is directly given into the circulation of the animal. 30 min after i.p. injection of HSA preparations containing stabilizers a small decrease of serum bilirubin concentration could be recognized. It was less pronounced and less persisting than after s.c. injection. Probably equilibration of HSA between peritoneum and plasma went on faster than between skin and plasma. Only for a short period a lack of albumin binding sites in the plasma of the rat pointed to a surplus of Na N-acetyl- dl -tryptophan.     

THE MOLECULAR CONTROL OF ANGIOGENESIS

Angiogenesis is a key event in a broad range of pathological conditions including both diseases with an enhanced and insufficient angiogensis. Angiogenesis is often intiated with vasodilation accompanied by an increase in vascular permeability. After destabilization of the vessel wall and degradation of the surrounding extracellular matrix, extravasation of plasma proteins provides a provisional scaffold for the migration of endothelial cells. Endothileal cell proliferation and migration themselves are under tight control by a balance of angionenesis inducers and inhibitors. A large number of angiogenic factors work together in a highly coordinated manner to induce endothelial cell outgrowth and the formation of functional vessels. On the other hand, angiostatic factor may play a critical role in the pathogenesis of ischemic diseases and contribute to the temination of physiological angiogenesis. Angiogenesis ends with the recruitment of pericytes and smooth muscle cells, which stabilize the newly formed vessel. The rapid increase in the knowledge about the molecular mechanisms of angiogenesis has led to first treatment trials in diseases with both enhanced and reduced angiogeneis. Although initial results are promising, much more work has to be done to consdier anti-angiogenic or pro-angiogenic approaches as reliable therapeutic tools.     

Prevalence of Hyperglycaemia and Undiagnosed Diabetes Mellitus in Patients with Acute Myocardial Infarction

ABSTRACT The prevalence of hyperglycaemia and undiagnosed diabetes mellitus was assessed in 214 consecutive patients admitted to the coronary care units with acute myocardial infarction (AMI). On admission, 16 patients (7.5%) had known diabetes, and 19 patients, not previously known to be diabetic, had blood glucose concentrations of ≥9 mmol/1. Fifteen patients survived for 2 months at which time a 75 g oral glucose tolerance test showed diabetes in 9 (60%) and impaired glucose tolerance in 4 (27%). Ten of these 13 patients (77%) with abnormal glucose tolerance had elevated glycosylated haemoglobin (HbA_1c) on admission, indicating pre-existing glucose intolerance or diabetes. The prevalence of undiagnosed diabetes was 4.5% (9/198). However, we may have overlooked undiagnosed diabetes in a small number of patients on admission, since only a random blood glucose <8 mmol/1 rules out diabetes, WHO criteria. Elevated blood glucose in patients with AMI is more likely to reflect a stationary pre-existing abnormal glucose tolerance than a temporary stress-induced phenomenon.     

Timing of the Upper Limit of Vulnerability is Different for Monophasic and Biphasic Shocks: Implications for the Determination of the Defibrillation Threshold

The upper limit of vulnerability (ULV) has been used in clinical studies to predict the DFT in patients with ICDs. Despite the ULV-DFT correlation, uncertainties about the optimal timing of the ULV determination remain. Previous studies using monophasic or biphasic shock waveforms reported differences in the ULV timing with respect to the electrocardiographic T wave. The purpose of this study was to directly compare the ULV timing for mono- versus biphasic T wave shocks. In ten isolated rabbit hearts, mono- and biphasic shocks were delivered randomly during the vulnerable window and at varying shock strengths to determine the ULV. The ULV timing was expressed as the coupling interval at the ULV, the myocardial repolarization state at the ULV measured by monophasic action potential recordings, and the relation between the ULV and the peak of the simultaneously recorded volume conducted T wave. The ULV for biphasic shocks occurred at longer coupling intervals than for monophasic shocks (188.0 ± 9.5 ms vs 173.5 ± 8.8 ms, P < 0.001). This resulted in a more repolarized myocardial state at the ULV for biphasic than for monophasic shocks (81.1%± 7.5% vs 66.9%± 9.0%, P = 0.002). The ULV for monophasic shocks occurred predominantly during the upslope of the T wave (8.0 ± 9.7 ms before the peak of the T wave) whereas the ULV for biphasic shocks occurred at or after the peak of the T wave (5.9 ± 9.3 ms after the peak of the T wave) (P < 0.001). Biphasic shocks delay the timing of the ULV as compared to monophasic shocks. This is important for the prediction of the DFT by ULV measurements.     

Tissue Distribution and Toxicokinetics of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Rats after Intravenous Injection

Tissue Distribution and Toxicokinetics of 2,3,7,8-Tetrachlorodibenzo-p-dioxinin Rats after Intravenous Injection. WEBER, L. W. D., ERNST,S. W., STAHL, B. U., AND ROZMAN, K. (1993). Fundam. Appl. Toxicol.21, 523–534. Male Sprague-Dawley rats (240–290 g) received intravenouslya nonlethal (9.25 µg/kg) or a lethal (72.7 µg/kg)dose of ¹⁴C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)administered as an emulsion. Animals were euthanized between5 min and 16 days (lethal dose) or 32 days (nonlethal dose)after treatment. Tissue distribution was considered completeafter 24 hr, as by this time radioactivity levels in white adiposetissue had reached a maximum. The highest levels of radioactivitywere found in liver (5% of dose/g tissue), followed by whitefat (1% of dose/g tissue); serum was lowest at 0.01% of dose/mlserum. Relatively high levels of radioactivity were also detectedin most known target organs of TCDD toxicity, e.g., brown fat,adrenals, and thyroid. The pattern of organ distribution ofTCDD was essentially the same after the lethal and the nonlethaldose, but did not follow a simple lipophilicity relationship,as levels in liver were higher than those in white fat, andthose in brain were extremely low. A pool of TCDD in liposomesinitially trapped in lung and spleen was redistributed within24 hr mainly to liver and adipose tissue. Affinity of TCDD tostorage fat seemed to play a more important role as a drivingforce for redistribution than did induction of cytochrome P4501A2. The terminal slope of elimination of TCDD from tissuesindicated a half-life of 16 days after the nonlethal dose. Afterthe lethal dose radioactivity declined in all tissues for 2to 8 days and then increased again, reflecting shrinking tissuevolumes as well as remobilization of TCDD caused by the processof body mass wasting. Distribution data for 17 tissues and serumwere subjected to regression analysis and resulted in up totwo uptake phases and up to three elimination phases for a giventissue. After the nonlethal dose TCDD was mainly excreted viafeces; combined urinary and fecal excretions occurred with abiological half-life of 16.3 ± 3.0 days. Much longerhalf-lives were detected in white fat and skin. After the lethaldose, the fecal excretion of TCDD-derived radioactivity decreasedafter 8 days, and urinary excretion increased starting 12 daysafter dosing. Radioactivity in liver and white fat and the extractableportion in feces was mainly unchanged TCDD, as determined bythin-layer chromatography. Radioactivity in urine indicatedthe presence of a metabolite(s) of TCDD only.