Scaphoid nonunion with carpal ligament injury - radiological, arthroscopical assessment and clinical results.

The purpose of this study was to review the clinical results of carpal ligaments injuries with scaphoid nonunion. We hypothesized that scaphoid nonunion with carpal ligament injury is associated with clinical result. We retrospectively reviewed 60 cases of -Herbert screw fixation with bone graft for scaphoid nonunions. Scapholunate (SL) and lunotriquetral (LT) ligaments lesions were confirmed by arthroscopy. Approximately half of the nonunion scaphoid cases had carpal ligaments injuries. At final follow-up evaluation, wrist function as evaluated by the Mayo wrist score was excellent in 34 patients, good in 16 patients, fair in 8 patients, and poor in 2 patients. Cases with both SL/LT ligaments injuries tended to have decreased wrist flexion-extension motion. Our results suggest that there is an indication for arthroscopy in scaphoid nonunion if surgical fixation is offered to avoid detrimental effects of an undiagnosed ligament tear.

Effects of depression and inflammatory factors on chronic conditions of the wrist.

AIMS: Chronic conditions of the wrist may be difficult to manage because pain and psychiatric conditions are correlated with abnormal function of the hand. Additionally, intra-articular inflammatory cytokines may cause pain. We aimed to validate the measurement of inflammatory cytokines in these conditions and identify features associated with symptoms. PATIENTS AND METHODS: The study included 38 patients (18 men, 20 women, mean age 43 years) with a chronic condition of the wrist who underwent arthroscopy. Before surgery, the Self-Rating Depression Scale (SDS), Hand20 questionnaire and a visual analogue scale (VAS) for pain were used. Cytokine and chemokine levels in the synovial fluid of the wrist were measured using enzyme-linked immunosorbent assays and correlations between the levels with pain were analysed. Gene expression profiles of the synovial membranes were assessed using quantitative polymerase chain reaction. RESULTS: Older patients had high pre-operative Hand20 scores. One-year post-operative Hand20 and VAS scores and pre-operative VAS scores correlated with SDS scores. Post-operative VAS scores negatively correlated with the expression of nerve growth factor and SDS scores positively correlated with the expression of tumour necrosis factor-alpha and negatively correlated with the expression of tumour necrosis factor-converting enzyme. CONCLUSION: There was a positive correlation between depression and chronic conditions of the wrist. Levels of some cytokines correlate with pain and depression. Additionally, cytokines may be important in the assessment and treatment of chronic conditions of the wrist and depression. Cite this article: Bone Joint J 2016;98-B:961-8.

Pelvic organ cross-sensitization to enhance bladder and urethral pain behaviors in rats with experimental colitis.

Neural cross-sensitization has been postulated as a mechanism underlying overlaps of chronic pelvic pain disorders such as bladder pain syndrome/interstitial cystitis (BPS/IC) and irritable bowel syndrome (IBS). Animals with experimental colitis have been used to study the underlying mechanisms for overlapped pelvic pain symptoms, and shown to exhibit bladder overactivity evidenced by frequent voiding; however, it has not directly been evaluated whether pain sensation derived from the lower urinary tract is enhanced in colitis models. Also, the cross-sensitization between the colon and urethra has not been studied previously. In the present study, we therefore investigated pain behaviors induced by nociceptive stimuli in the lower urinary tract and the involvement of C-fiber afferent pathways using rats with colitis induced by intracolonic application of 2,4,6-trinitrobenzenesulfonic acid (TNBS). In TNBS-induced colitis rats at 10 days, intravesical application of resiniferatoxin (RTx) induced a significantly greater number of episodes of both licking and freezing behaviors, which were reduced by capsaicin-sensitive C-fiber afferent desensitization. Histochemical studies using fluorescent dye tracers injected into the colon, bladder or urethra showed that dichotomized afferent neurons comprised 6.9-14.5% of L1, L6 and S1 dorsal root ganglion (DRG) neurons innervating the colon or the lower urinary tract. Transient receptor potential vanilloid 1 (TRPV1) mRNA expression was significantly increased in, the bladder, urethra and S1 DRG in colitis rats. An increase in myeloperoxidase (MPO) activity was found in the colon, but not in the bladder or urethra after intracolonic TNBS treatment. These results indicate that TNBS-induced colitis increased pain sensitivity in the bladder and urethra via activation of C-fiber afferent pathways due to colon-to-bladder and colon-to-urethral cross-sensitization, suggesting the contribution of pelvic organ cross-sensitization mechanisms to overlapped pain symptoms in BPS/IC and IBS.

Effect of herpes simplex virus vector-mediated interleukin-4 gene therapy on bladder overactivity and nociception.

We investigated the effects of replication-defective herpes simplex virus (HSV) vector expression of interleukin-4 (IL-4) on bladder overactivity and nociception. HSV vector expressing murine interleukin-4 (S4IL4) or the control vector expressing ß-galactosidase (SHZ) were injected to the rat bladder wall. At 1 week after viral injection, in cystometry performed under urethane anesthesia, the S4IL4-treated group did not show the intercontraction intervals reduction during intravesical administration of 10 nM resiniferatoxin (RTx). At 2 weeks after viral injection, behavioral studies were performed on vector-injected animals in an awakened state. Freezing behavior induced by 3 µM RTx, administered for 1 min into the bladder, was significantly suppressed in the S4IL4 group compared with the SHZ group. Murine IL-4 levels examined by ELISA were significantly increased in bladder and bladder afferent dorsal root ganglia at 2 weeks after viral injection. The expression of IL-1ß and IL-2 and bladder inflammatory responses were significantly suppressed in the RTx-irritated bladder of S4IL4-injected rats. These results indicate that HSV vector-mediated interleukin-4 expression in the bladder and bladder afferent pathways reduces the inflammatory response, bladder overactivity and nociceptive behavior induced by bladder irritation in the rat model. Therefore, IL-4 gene therapy could be a new strategy for treating urinary frequency and/or bladder pain.

Isoflurane and sevoflurane during reperfusion prevent recovery from ischaemia in mitochondrial KATP channel blocker pretreated hearts.

BACKGROUND AND OBJECTIVE: Inhalation anaesthetics given only during post-ischaemic reperfusion have some protective effect against reperfusion injury in the heart. Adenosine triphosphate-regulated mitochondrial potassium channels have been shown to be an important mediator of cardioprotection. Thus, we investigated whether 5-hydroxydecanoate, a putative mitochondrial potassium channel blocker, prevents the cardioprotective effect of volatile anaesthetics. METHODS: Forty rats were randomly allocated to four groups of equal size: control group, 5-hydroxydecanoate group, 5-hydroxydecanoate + sevoflurane group and 5-hydroxydecanoate + isoflurane group. Seven minutes after the start of perfusion, normal saline (control group) or 5-hydroxydecanoate (the other groups) was administered. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min. One minute before the end of the ischaemic period, 2.7% sevoflurane or 1.4% isoflurane were administered in the 5-hydroxydecanoate + sevoflurane or 5-hydroxydecanoate + isoflurane groups respectively. The heart was reperfused for 10 min. RESULTS: Adenosine triphosphate content at the end of reperfusion in the 5-hydroxydecanoate + sevoflurane group was significantly lower (P < 0.05) than those in the control and the 5-hydroxydecanoate + isoflurane groups (19.9 +/- 8.7, 28.1 +/- 3.4 and 30.4 +/- 2.3 micromol g(-1), respectively). In addition, the combination of inhalation anaesthetics and 5-hydroxydecanoate decreased the ratios of recovered hearts from ischaemia (5-hydroxydecanoate + sevoflurane group: 40%, 5-hydroxydecanoate + isoflurane group 50%). CONCLUSION: 5-hydroxydecanoate alone caused no significant changes in haemodynamics and myocardial metabolism. However, the combination of 5-hydroxydecanoate and volatile anaesthetics impaired the recovery from ischaemia. Although animal data cannot be extrapolated to human beings, we suggest that more attention be paid to patients on sulphonylurea drugs, which inhibit potassium channels, when they are anaesthetized with volatile anaesthetics.

Laceration of gastric mucosa associated with dialysis-related amyloidosis.

We report a 72-year-old female on long-term hemodialysis, who was admitted to the hospital because of hematemesis. On emergency laparotomy, pylorogastrectomy was performed. The resected specimen showed a giant hematoma and traversing fissure along the lesser curvature of the body of the stomach. Histologically, the specimen showed wide hematoma formation and amyloid deposits in the submucosal layer, especially in the wall of blood vessels. These deposits reacted positively to antihuman beta2-microglobulin antibody. The post-operative course was favorable, and the patient was discharged on the 35th hospital day. In this case, the laceration site on the gastric mucosa was almost intact and did not demonstrate ischemic change, suggesting that the giant hematoma was caused by submucosal vessel rupture, which led to the gastric mucosa laceration. To our knowledge, this is the first case of gastric mucosa laceration associated with dialysis-related amyloidosis.

Importance of transition zone prostate biopsies in patients with gray-zone PSA levels undergoing the ultrasound-guided systematic ten-biopsy regimen for the first time.

INTRODUCTION: We analyzed the efficacy of routine transition zone biopsies for patients undergoing ultrasound-guided systematic prostate biopsies for the first time because of an elevated serum prostate-specific antigen (PSA) level. PATIENTS AND METHODS: Using the systematic ten-biopsy regime, four additional transition zone biopsies were performed in 236 consecutive patients, because they showed an elevated PSA level (range 4.0- 9.9 ng/ml). RESULTS: The overall prostate cancer detection rate was 21.2% (50/236). In 24 patients (48.0%), cancers were detected only in the peripheral zone, in 4 (8.0%) only in the transition zone, and in 22 (44.0%) in both zones. No distinguishing characteristics could be determined for the cancers detected in the transition zone only. CONCLUSIONS: Although the cancer detection rate for the transition zone was significantly lower than for the peripheral zone, it was higher than that reported in most other studies which may have included biopsy specimens from patients with advanced prostate cancers. The usefulness of transition zone biopsies for the detection of early-stage prostate cancer, especially in patients with a PSA gray zone, can, therefore, not be denied.

High sensitivity of PCR in situ hybridization for the detection of human papillomavirus infection in uterine cervical neoplasias.

OBJECTIVE: This study was designed in order to examine whether the sensitivity of PCR in situ hybridization (PISH) is superior to that of fluorescence in situ hybridization (FISH) and immunocytochemical staining (ICS) in detecting the presence of human papillomavirus (HPV) infection in uterine cervical neoplasias. METHODS: Three cell specimens were obtained from every 54 patients who had been histologically and cytologically diagnosed as severe dysplasia of the uterine cervix (SD), carcinoma in situ of the uterine cervix (CIS), or microinvasive carcinoma of the uterine cervix (MIC). All of them were first stained by the Papanicolaou (pap) method before the experiments. After specimens were classified into SD (n = 17) and CIS/MIC groups (n = 37), the sensitivities of detection for HPV infection were compared among PISH, FISH, and ICS methods which had been carried out after decolorization of the pap stain. RESULTS: In the SD group, PISH demonstrated a 58.8% positive incidence of HPV, which was significantly higher than that (23.5%) shown by FISH (P < 0.05). There was no significant difference in the positivities of HPV between the PISH and ICS (47.1%) methods. In the CIS/MIC group, PISH, FISH, and ICS showed 73.0, 43.2, and 54.1% positive incidences of HPV, respectively. There was significant difference in HPV positivities between PISH and FISH as well as ICS (P < 0.01, P < 0.05). The total frequency of the detection of HPV infection by PISH was significantly higher than that by FISH (P < 0.01) and high with a marginal significance compared to that by ICS (P = 0.051). Moreover, the morphologic change of a single cell and the HPV-positive signals could be observed simultaneously by the PISH technique. CONCLUSION: Because PISH possesses high sensitivity for the detection of HPV infection in morphologically intact cells from uterine cervical neoplasia, the PISH technique might have promising potential for application to the detection of HPV presence in situ in screening.

Usefulness of PCR in situ hybridization as a technique for morphological detection of human papillomavirus in uterine cervical neoplasia.

This study was designed in order to devise fitting conditions in polymerase chain reaction (PCR)-in situ hybridization (ISH) for observing human papillomavirus (HPV) infection morphologically in uterine cervical neoplasias and to compare the detection rates of HPV by PCR-ISH and solution phase PCR (S-PCR) as well as fluorescence ISH (FISH). Tissues were obtained from 23 patients with cervical intraepithelial neoplasia 3, who visited our hospital between 1994 and 1997. To detect HPV-16, a HPVpF forward primer and a HPVp 16 reverse primer were used. Compared with the traditional methods, the PCR-ISH technique performed in this study was contrived as follows. To prevent detachment, the specimens were attached to silane-coated slides at 90 degrees C and successively left at room temperature for 36 hours. In proteopepsis, pepsin was used. PCR products were fixed with 4% paraformaldehyde. PCR-ISH, S-PCR, and FISH showed HPV-16 positivity in 52.2%, 56.5% and 21.7%, respectively. The positive rate of HPV-16 detected by PCR-ISH as well as S-PCR was significantly higher than that by FISH (p<0.01, respectively). There was no significant difference between the positive rates of HPV-16 detected by PCR-ISH and S-PCR. HPV-16 was detected by S-PCR in all 12 specimens in which HPV-16 expression was judged as positive using PCR-ISH. Similarly, HPV-16 was found by PCR-ISH in all five specimens in which HPV-16 expression was regarded as positive using FISH. While the FISH technique detected HPV-16 signals only in the superficial and middle layers of squamous cells, the PCR-ISH technique demonstrated them in all the layers including the parabasal and basal layers. The PCR-ISH technique contrived in this study has a high sensitivity to HPV-16 equal to that of S-PCR. The difference in detection rate and distribution of HPV DNA between PCR-ISH and FISH might suggest that HPV does not infect the superficial layer but rather the parabasal layer.

Urinary excretion of the vitronectin receptor (integrin alpha V beta 3) in patients with Fabry disease.

A renal disorder is one of the important manifestations of Fabry disease, but the details of the pathogenesis have not been clarified yet. We examined the possibility that the vitronectin receptor (VNR, integrin alpha V beta 3), one of the integrins, is involved in the progression of the renal injury in Fabry disease. We measured the urinary excretion of beta 3 originating from VNR in Fabry patients by immunoblotting analysis and enzyme-linked immunosorbent assay (ELISA). Immunofluorescent microscopic analyses for VNR and globotriaosylceramide were performed on urinary sediments from Fabry patients. Furthermore, beta 3 and vitronectin in kidney tissues were analyzed immunohistochemically. Immunoblotting analysis and ELISA showed that the urinary excretion of beta 3 originating from VNR was significantly increased in the Fabry group compared with both the pathological and healthy control groups. Immunofluorescent microscopy revealed the expression of VNR and accumulation of globotriaosylceramide in urinary sediments from the Fabry patients. Increased expression of beta 3 was observed in glomerular epithelial cells, and in Bowman's capsular epithelial layer and tubular cells, and the amount of vitronectin was moderately increased in the kidney tissues from the Fabry patients. The urinary excretion of VNR was increased, and the expression of VNR was observed in Fabry kidney tissues. The expression of VNR may be involved in the progression of the renal injury in this disease.

A case of mitochondrial cytopathy with a typical point mutation for MELAS, presenting with severe focal-segmental glomerulosclerosis as main clinical manifestation.

A 27-year-old female with short stature and mild hearing loss was diagnosed as having focal-segmental glomerulosclerosis by renal biopsy at our hospital. One year later she developed progressive renal dysfunction and cardiac failure and was admitted again to our hospital for evaluation. Though her only neurological disorder was mild hearing loss, her short stature and elevated lactate and pyruvate values in cerebrospinal fluid suggested mitochondrial cytopathy. A muscle biopsy specimen of the left biceps brachii, using modified Gomori trichrome stain, showed a typical image of ragged-red fibers, and an increased number of giant mitochondria with paracrystalline inclusions were visible by electron microscopy. Mitochondrial DNA from the skeletal muscle showed an A-to-G transition at 3243 of transfer RNALeu(UUR), the common point mutation for mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. These data confirmed the diagnosis of atypical mitochondrial cytopathy with renal and heart involvement. Mitochondrial cytopathies are often associated with hypertrophic cardiomyopathy but rarely with renal disease. Among the few reported cases with associated renal disease, most included renal tubular disorders; few cases with focal glomerular sclerosis are known. The present case of atypical mitochondrial cytopathy was characterized by a unique clinical course and rare complications with focal-segmental glomerulosclerosis.

Comparative effects of Ringer's acetate and lactate solutions on intraoperative central and peripheral temperatures.

STUDY OBJECTIVES: To compare the effects of Ringer's lactate (LR) and Ringer's acetate (AR) solutions on core body and peripheral temperatures during isoflurane or sevoflurane anesthesia. DESIGN: Prospective, randomized study. SETTING: Operating rooms of a university hospital. PATIENTS: 60 ASA physical status I and II patients undergoing general surgery. INTERVENTIONS: Following induction with 5 mg/kg of thiamylal and 0.1 mg/kg of vecuronium, patients were randomly assigned to one of four groups (15 patients per group). They received inhalation anesthetics (66% nitrous oxide [N2O] and 1.0% to 2.0% isoflurane or 1.3% to 2.6% sevoflurane) and LR or AR. MEASUREMENTS AND MAIN RESULTS: Tympanic membrane (central) temperatures, forearm temperatures, and fingertip temperatures were recorded during surgery every 30 minutes. Tympanic membrane temperatures in the patients given AR were significantly higher than those given LR during isoflurane anesthesia 5 and 30 minutes after induction of anesthesia. However, this was not the case for sevoflurane anesthesia. There were no significant differences in forearm and fingertip temperatures or fingertip bloodflow among the four groups. CONCLUSION: There was no significant difference between AR and LR in the preservation of heat during either sevoflurane or isoflurane anesthesia. However, AR may be superior to LR for maintaining central temperature during the early period of isoflurane anesthesia.

Isolation and characterization of the yeast las21 mutants, which are sensitive to a local anestheticum, tetracaine.

We isolated and characterized yeast mutants whose growth is sensitive to a local anestheticum tetracaine and, at the same time, temperature sensitive. These mutants were collectively called las mutants (local anestheticum sensitive). The las21 mutants were analyzed in this study. The wild type LAS21 gene was cloned by exploiting temperature sensitivity of the las21 mutants and we found that LAS21 encodes ORF YJL062w which has not been analyzed before. Las21p is putative membrane protein belonging to the major facilitator super family containing plural membrane spanning domains. Complete elimination of the LAS21 ORF did not kill the cells but made their growth temperature sensitive. Interestingly, the complete loss of the LAS21 gene canceled the sensitivity to tetracaine. The ability of the las21 mutants to grow at a higher temperature was recovered in the various media containing an osmotic stabilizer or salts. Furthermore, temperature sensitivity of the las21 mutants was partially suppressed by introduction of PKC1, encoding protein kinase C, on a high copy vector. We found some genetic interactions between LAS21 and Ras/cAMP cascade genes. These results suggest that LAS21 defines unknown pathway regulating the stress response of yeast.

Immunological analysis of organized pneumonia with eosinophilic pleural effusion.

A 73-year-old man developed organized pneumonia with severe right-sided eosinophilic pleural effusion (PE). CD69+ and HLA-DR+ eosinophils in PE were 90 and 31%, respectively, but were undetectable in peripheral blood (PB). CD4+, CD45RA+ (naive) and CD4+, CD45RO+ (memory) cells in PB, PE and bronchoalveolar lavage (BAL) were 10.9, 8.4, 2.5 and 22.7, 38.3 and 16.4%, respectively. CD8+, CD45RA+ (naive) and CD8+, CD45RO+ (memory) cells in PB, PE and BAL were 3.5, 4.7, 1.0, and 8.9, 11.3 and 46.0%, respectively. The concentrations of interleukin-5 (IL-5) and IL-6 in PE were 1,680 and 2,797 pg/ml, respectively; however, these cytokines were undetectable in PB. The patient died 1 month after surgery to remove right thickened pleura. Microscopic findings showed right fibrinous pleuritis and organized pneumonia.

Association between the extent of sclerotic changes in iliac arteries and long-term prognosis in patients with ischemic heart disease.

Peripheral vascular disease is often complicated with ischemic heart disease and is associated with increased cardiac mortality. Latent progression of sclerotic changes in the arteries supplying the lower extremities is often present but undiagnosed. We examined the influence of sclerotic changes of the iliac arteries on the late outcome in 79 patients with ischemic heart disease. Lower abdominal aortography was performed at the time of cardiac catheterization between December 1989 and January 1991. The degree of sclerotic change in the iliac arteries was assessed according to aortography findings such as stenosis, dilatation or bend, with higher scores representing more advanced sclerosis (aortography score). The mean aortography score of all patients was 5.8 +/- 4.6. The patients were followed up for 4.4 +/- 1.2 years to monitor the occurrence of cardiac events (cardiac death, acute myocardial infarction, coronary bypass surgery, or coronary angioplasty for new lesion). The cardiac event-free rate at 5 years was 76.6% in the high score group (32 patients with scores of 6 or more) and 92.9% in the low score group (47 patients with scores of 5 or less). The difference was significant (p = 0.007) by log-rank test. The hazard rate of the aortography score for predicting risk of cardiac event was 1.11 by the Cox proportional hazards model (95% confidence intervals: 1.01-1.23, p = 0.039). When the analysis was adjusted for coronary bypass surgery as primary therapy, the number of diseased coronary arteries, or the presence of peripheral vascular disease, similar results were obtained. In conclusion, more severe sclerotic change in iliac arteries is associated with a higher incidence of cardiac events in patients with ischemic heart disease.

Acute presynaptic inhibition by doxorubicin of negative chrono- and inotropic responses to parasympathetic nerve stimulation in isolated, blood-perfused dog atrium.

The clinical use of doxorubicin, an anthracycline antineoplastic agent, is limited by its cardiotoxicity. Although several previous reports have shown neurotoxic effects of doxorubicin, there is little information about the acute effects of doxorubicin on the autonomic nerve functions in the heart. Accordingly, to evaluate the effects of doxorubicin on the cardiac responses to autonomic nerve activation, we studied the effects of doxorubicin on the negative chrono- and inotropic responses to intracardiac parasympathetic nerve stimulation and acetylcholine (ACh), and the positive chrono- and inotropic responses to norepinephrine (NE) in the isolated, blood-perfused dog atrium. Doxorubicin (0.01-3 mumol), injected into the sinus node artery of the isolated atrium, induced negative inotropic effects dose dependently and weak negative chronotropic effects. Doxorubicin inhibited the negative chrono- and inotropic responses to parasympathetic nerve stimulation dose dependently. However, doxorubicin affected neither the negative chrono- and inotropic responses to ACh nor the positive chrono- and inotropic responses to NE. These results indicate that doxorubicin interacts with neither muscarinic receptors nor beta-adrenoceptors and suggest that doxorubicin inhibits the negative cardiac responses to parasympathetic nerve activation due to the inhibition of ACh release from nerve varicosities in the heart.

[Anesthesia with transesophageal echocardiography for removal of pheochromocytoma].

A 45-year-old female was scheduled for left adrenalectomy because of a pheochromocytoma. Preoperative general condition was well controlled with alpha- and beta-blockers. Anesthesia was induced with thiamylal and vecuronium, and maintained with isoflurane (0.5-3%) and nitrous oxide in oxygen. Blood pressure was controlled with nicardipine and alpha-blocker during the manipulation of the tumor. After removal of the tumor, dopamine and norepinephrine were used. We used transesophageal echocardiography (TEE) to determine the fluid administration rate and doses of catecholamine. We could observe the wall motion and the mass of the heart, and see changes of the left ventricular enddiastolic volume, the cardiac output and the stroke volume. TEE monitoring seems to be very useful during the resection of pheochromocytoma.

[Aplastic anemia complicated with secondary hemochromatosis after allogenic bone marrow transplantation].

We report a case of aplastic anemia complicated with secondary hemochromatosis after allogenic bone marrow transplantation (BMT). A 29-year-old man was diagnosed as having aplastic anemia at the age of 8. At the age of 28, BMT was performed from his HLA-identical sister. Total volume of blood transfusion before BMT was about 28,000 ml, and in three months after BMT was 8,000 ml. The transplantation was successful, but one month after BMT, dry eyes, skin pigmentation and hepatomegaly appeared. Serum bile duct enzymes and ferritin also increased remarkably. Moreover after thirteen months, glucose tolerance impaired seriously. Abdominal computed tomography (CT) revealed atrophic pancreas and an increased CT density in the liver and the tail of the pancreas. A large amount of iron deposition were also found in liver and stomach biopsy specimens. We concluded that diabetes mellitus was due to secondary hemochtomatosis in the present case. There is a possibility that tissue damage due to iron deposits may have been accelerated through BMT in this patient with a history of many blood transfusions.

Comparative effects of halothane, enflurane, isoflurane and sevoflurane on function and metabolism in the ischaemic rat heart.

This study was designed to examined the effects of inhalation anaesthetics on function and metabolism in isolated ischaemic rat hearts. Four volatile anaesthetics in two different concentrations (1.0 to 1.5 MAC) were used before whole heart ischaemia was induced for 15 min followed by reperfusion for 30 min. The data were compared with a control group in which inhalation anaesthetics were not used. Before ischaemia, volatile anaesthetics depressed ventricular function. During reperfusion, ventricular function and coronary flow in both halothane groups were significantly lower than those in the control group. Myocardial ATP concentrations in the 1.0 MAC of enflurane and isoflurane groups were significantly higher than those in the control group. We conclude that halothane had more depressant effects than the other anaesthetics and that enflurane and isoflurane may enhance metabolic recovery in the ischaemic working rat heart.

Are negative chronotropic and inotropic responses to adenosine differentiated at the receptor or postreceptor levels in isolated dog hearts?

Inhibition by zatebradine, a specific bradycardic agent, of the negative inotropic but not chronotropic responses to adenosine has been briefly reported in the isolated, perfused dog heart. We therefore investigated whether subtypes of adenosine receptors or postreceptor transduction mechanisms differentiated the negative chronotropic and inotropic responses to adenosine in the isolated, blood-perfused atrial and ventricular preparations of the dog. Adenosine (1-3000 nmol), adenosine A1 receptor agonists, 2-chloroadenosine (CAD, 0.1-300 nmol) and N6-cyclohexyladenosine (CHA, 1-300 nmol) and a nonselective adenosine receptor agonist, 5'-N-ethyl-carboxamidoadenosine (NECA, 0.1-100 nmol), induced the negative chronotropic and inotropic responses. The potency order was NECA > CAD > adenosine > or = CHA. An adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10-300 nmol), dose-dependently inhibited the negative chronotropic and inotropic responses to adenosine, CAD and NECA in the isolated, perfused right atrium. DPCPX also blocked the negative inotropic responses to adenosine, CAD and NECA in the isolated left ventricle. However, an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX, 300 nmol), did not affect the negative cardiac responses to adenosine and NECA. Although the negative inotropic but not chronotropic responses to CAD and adenosine were dose-dependently inhibited by zatebradine, K+ channel inhibitors 4-aminopyridine and E-4031 did not modify the cardiac responses to adenosine and CAD. These results suggest that the negative cardiac responses to adenosine are mediated by adenosine A1 receptors and the negative chronotropic and inotropic responses to adenosine are differentiated at the postreceptor transduction level(s) in the dog heart.