Changes in arterial levels and myocardial metabolism of catecholamines during pacing-induced angina pectoris.

In order to elucidate the effects of atrial pacing on cardiac catecholamine metabolism, 11 patients were studied during cardiac catheterization. Blood samples were drawn from a peripheral artery and the coronary sinus for estimation of catecholamine concentrations. Heart rate was increased by 10 beats/min each minute, and all patients experienced chest pain at maximal pacing rate. Coronary sinus blood flow rose from 122 +/- 19 at rest to 208 +/- 25 ml/min at final pacing rate, and myocardial lactate extraction ratio decreased. There was no significant change in arterial epinephrine levels, whereas the extraction ratio decreased (p less than 0.05). The norepinephrine arterial levels increased at the final pacing rate (p less than 0.01). The calculated myocardial release increased as well, but not to a statistically significant degree. The exact mechanisms of the rise in sympathetic activity and arterial norepinephrine levels cannot be ascertained with the present study design. Myocardial ischemia with subsequent chest pain seems to be a probably cause for the increased sympathetic outflow.     

Ropivacaine 0.25% and 0.5%, but not 0.125%, provide effective wound infiltration analgesia after outpatient hernia repair, but with sustained plasma drug levels

BACKGROUND AND OBJECTIVES: Ropivacaine is a long-acting local anesthetic similar to bupivacaine, but with lower cardiac toxicity and intrinsic vasoconstrictive properties that may reduce the risk and extent of systemic plasma absorption. Plasma levels and risks are associated with the total dose used and the extent of absorption, with lower doses potentially representing less risk. Although both 0.5% and 0.75% ropivacaine provide adequate analgesia for wound infiltration after hernia repair, the efficacy of lower doses and the early systemic absorption have not been reported. METHODS: We studied postoperative pain and systemic plasma levels following either the injection of 30 mL of saline or 0.125%, 0.25%, or 0.5% ropivacaine into the wounds in 110 healthy patients following hernia repair under spinal anesthesia. Pain was assessed using visual analog scale (VAS) scores and algometer readings at rest and after coughing, and oral analgesic requirements were assessed in the first 5 hours after surgery and for the week after discharge. RESULTS: Both 0.25% and 0.5% ropivacaine provided pain relief following surgery when compared with saline or 0.125%. No adverse reactions to the drug were reported in any group. Plasma levels of ropivacaine peaked between 30 and 60 minutes, at 0.109, 0.249, and 0.399 mg/L for 0.125%, 0.25%, and 0.5% concentrations, respectively. Although the levels were below those producing clinical symptoms, they remained elevated for the entire 2-hour sampling period. This implies an absorption-dependent elimination which is substantially longer than reported with other routes of injection. CONCLUSIONS: Ropivacaine 0.25% and 0.5% is adequate for pain relief after outpatient hernia repair, whereas the 0.125% solution is no more effective than saline. Prolonged systemic absorption from peripheral injection may be associated with prolonged elevations of plasma concentrations, which potentially could be associated with unexpectedly high plasma levels if repeated injections are performed in the perioperative period with higher concentrations or doses.     

Improved blood compatibility of a stent graft by combining heparin coating and abciximab

The aim of this study was to assess the combined effect of heparin coating of a stent graft and administration of abciximab, on platelet and coagulation activity in vitro. METHODS: Stent grafts with an expanded polytetrafluoroethylene (ePTFE) membrane interfoliated between two stents were deployed in tubings to form Chandler loops. Fresh human blood with a low concentration of heparin and various doses of abciximab was rotated for 1 h, then collected and used for measurements of platelets, thrombin-antithrombin complex (TAT), CD11b, complement and contact activation of coagulation. In the first set of experiments, all stent grafts were heparin coated. There were three study groups: Group 1a (no abciximab, n=5); Group1b (abciximab in a concentration of 3.3 microg/ml, n=5); Group 1c (abciximab in a concentration of 8.3 microg/ml, n=5). In the second set of experiments, the concentration of abciximab was 3.3 microg/ml. There were three study groups: Group 2a (untreated stent grafts, n=4); Group 2b (heparin-coated stent grafts, n=4); Group 2c (heparin-coated PVC tubings with no stent grafts, n=4). RESULTS: In the first set of experiments, there was a significant reduction in platelet count in Group 1c compared to Group 1a and Group 1b. There was a significant reduction in TAT in Group 1b and Group 1c as compared to Group 1a. In the second set of experiments, TAT was reduced in Group 2b and Group 2c compared to Group 2a. Contact activation was lowered in Group 1b and Group 1c as compared to Group 1a for both FXIa-AT (0.088 and 0.088 vs. 0.115) and FXIIa-AT (0.12 and 0.12 vs. 0.19). CONCLUSION: Heparin coating of a stent graft was shown to improve blood compatibility and this was further enhanced by addition of abciximab.     

Tracing genotypes of mutans streptococci on tooth sites by random amplified polymorphic DNA (RAPD) analysis

The aim of this study was to clarify the distribution and persistence of mutans streptococci on different tooth sites in the same oral cavity. Thirteen subjects, aged 20-40 years, were examined. Salivary levels of mutans streptococci, caries prevalence, oral hygiene habits and status of tooth surfaces sampled were recorded. Plaque samples were obtained from four sites, the mesial and buccal surfaces of the first permanent molar on the right side of the lower jaw (46m and 46b), the distal surface of the first permanent premolar (24d) and the mesial surface of the second permanent premolar (25m) on the left side of the upper jaw, using sterile toothpicks on two occasions at 4-7-month intervals. The samples were cultivated on site-specific Strip mutans. Up to 10 colonies/site were isolated when present and genotyped by random amplified polymorphic DNA (RAPD) analysis, after species identification with PCR. Genotyping was also performed by restriction endonuclease analysis (REA) on 148 isolates, and results were consistent with the RAPD results. Most mutans streptococcus-positive samples were obtained from 46m. Within each individual, the same genotype occurred on at least two sites on all but one sampling occasion. A maximum of seven different genotypes were found in an individual. For a particular tooth site, four genotypes occurred simultaneously and taking both sampling occasions together the maximum was six different types. The same genotypes/types were found again after 4-7 months on 25 sites in 12 subjects. Fifteen sites were mutans streptococcus-positive on only one sampling occasion. The results indicate that several different genotypes of mutans streptococci colonize a tooth site, and that the same genotype colonizes several sites in the same oral cavity. Persistence of genotypes on a site for several months and interindividual differences in the occurrence of genotypes were also found.     

Hereditary prostate cancer: clinical characteristics and survival

PURPOSE: Hereditary prostate cancer accounts for 5% to 10% of all prostate cancer cases. We assessed clinical characteristics and survival in patients with hereditary prostate cancer MATERIALS AND METHODS: The study comprised 201 patients from 62 Swedish hereditary prostate cancer families and 402 controls with prostate cancer who were matched for age and calendar year at diagnosis, and the hospital where the diagnosis was made. Clinical data were obtained from the National Cancer Registry, Causes of Death Registry and medical records. RESULTS: Median age at the diagnosis of hereditary prostate cancer was 68 years, which was 6 years less than in patients with prostate cancer in the general population in Sweden. Distributions of tumor grade, symptoms at diagnosis and initial therapy were similar in hereditary prostate cancer cases and controls. More controls were classified with localized disease but it may have been due to methodological problems. Overall and cancer specific survival was similar in patients with hereditary prostate cancer and controls as well as in subgroup analyses including those with early onset and those diagnosed before 1990. Prostate cancer was the cause of death in 75% of patients with hereditary prostate cancer, in contrast to 55% with prostate cancer in the Swedish population. This difference was completely explained by the earlier age at the diagnosis of hereditary prostate cancer. CONCLUSIONS: Hereditary prostate cancer has an earlier onset than sporadic prostate cancer but this study did not indicate any other important difference in clinical characteristics or survival in patients with hereditary prostate cancer and those with sporadic prostate cancer. However, it cannot be excluded that individual hereditary prostate cancer genes may have specific biological characteristics.     

Benestent II: back to the future

It has been shown repeatedly in animal and clinical studies that heparin coating reduces thrombotic complications of several surfaces in contact with flowing blood. The demonstration that implantation of heparin-coated coronary stents is also effective in prevention of subacute thrombotic occlusion in a pig model offers the perspective of a clinical role of this treatment too. In order to put this to the test, the Benestent II pilot trial has been designed. This study will be conducted in a stepwise fashion in order to explore the feasibility of delaying deep anticoagulation as much as possible. Therefore, the primary goal is to minimize or exclude the need for heparin treatment following stent implantation. In addition, the effects on the need for revascularization procedures during follow-up will be recorded as well as the late morphological consequences as measured with quantitative coronary angiography.     

Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics

Summary Nifedipine capsules t.d.s. and an extended release formulation of nifedipine, nifedipine-ER tablets, given once daily in corresponding daily doses, have been compared with placebo in a double-blind, three-way crossover study in 24 patients with stable angina pectoris. The objective was to study the influence on the antianginal effect of the different pharmacokinetics of several preparations of nifedipine. All patients received concomitant treatment with -adrenoceptor blockers. Antianginal efficacy was assessed by a dynamic exercise test at the end of the dosage intervals, i.e. 8 and 24 h after nifedipine capsules and nifedipine-ER, respectively, as well as 6 h after dosing. Six h after dosing the time of onset of chest pain and total excercise time were longer and total work was significantly higher during both nifedipine-ER (plasma concentration 260 nmol/l) and placebo treatment than after nifedipine capsules (plasma concentration 78 nmol/l). Time to 1 mm ST depression was longer during nifedipine-ER than during nifedipine capsule treatment. No significant difference was seen between nifedipine-ER and placebo. At the end of the dosage interval (24 and 8 h after nifedipine-ER and nifedipine capsules, respectively), no significant difference was found between nifedipine-ER (plasma concentration 75 nmol/l) and the other two treatments. However, placebo was superior to nifedipine capsules (plasma concentration 58 nmol/l) both in the time to onset of chest pain and total exercise time. The lack of effect at the end of the dosage interval was probably due to the subtherapeutic plasma nifedipine level. Nifedipine capsules, but not the extended release formulation, were found to be significantly inferior to placebo both after 6 h and at the end of the dosage interval. This unexpected finding may have been induced by the rapid and extensive fluctuation in plasma levels, with a rapid decline from the peak value after the capsule formulation, since a similar deterioration was not seen with nifedipine-ER, despite similar plasma concentrations at the end of the dosage interval. This phenomenon merits further research.     

Effects of physical and apnea training on apneic time and the diving response in humans

The aim of this investigation was to study separately the effects of physical training and apnea training on the diving response and apneic time in humans. Both types of training have been suggested to lead to prolonged apneic time and an increased “diving response” (i.e., regional vasoconstriction and bradycardia). The study was also designed to examine the effects of these two types of training on the characteristics of the increase in apneic time with repeated apneas. Simulated diving tests were performed before and after the different training programs. The test format was one apnea and five apneas with facial immersion in cold water at 2-min intervals. An increase in apneic time was observed after physical training (n=24), and this was attributable to an increased time beyond the physiological breaking point. The other parameters that were measured remained unaffected. After apnea training (n=9), however, apneic time was increased by a delay in the physiological breaking point, which is mainly determined by the arterial tension of CO₂. The diving response had increased, and the effect of repeated apneas on apneic time tended to be larger after apnea training. These results may explain the pronounced diving responses and long apneas observed in trained apneic divers. Accepted: 3 February 2000     

The effect of transcutaneous electrical nerve stimulation (TENS) on catecholamine metabolism during pacing-induced angina pectoris and the influence of naloxone

Two invasive studies (invasive study I and invasive study II) showed positive effects of transcutaneous electrical nerve stimulation (TENS) in pacing-induced angina pectoris in terms of increased tolerance to pacing, improved lactate metabolism and less anginal pain. Invasive study I demonstrated a decrease in left ventricular afterload by TENS treatment as reflected by a fall in systolic blood pressure, and this fact was thought to be explained by reduced sympathetic activity since arterial levels of epinephrine and norepinephrine dropped during TENS in TENS responders. In invasive study II, the influence of naloxone on the effects of TENS in pacing-induced angina pectoris was studied in 11 patients with severe coronary artery disease. The patients were catheterized and treated with TENS on 2 occasions; one with a single intravenous (i.v.) dose of saline as placebo and one with a single i.v. dose of 50 mg naloxone, double-blind, in random order. Treatment with TENS increased tolerance to pacing (P less than 0.01 with placebo and P less than 0.01 with naloxone, respectively) and improved lactate metabolism (P less than 0.05 with placebo and P less than 0.01 with naloxone, respectively). The positive effects of TENS were thus reproducible and not reversed by single i.v. doses of naloxone. The results of this study indicate that the effects of TENS on the heart are not mediated by beta-endorphin but do not exclude activation of more short-acting opioids like delta or kappa receptor agonists (met-enkephalin and/or dynorphin) since naloxone has a low affinity for these receptors. It is also possible that non-opioid mechanisms are of importance.(ABSTRACT TRUNCATED AT 250 WORDS)