Biomedical subjects

M Gandhi

Publications and source records attributed to M Gandhi.

At least 19 recordsLinked to original sources

PubMed2006

Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements.

Recurrent chromosomal rearrangements are common in cancer cells and may be influenced by nonrandom positioning of recombination-prone genetic loci in the nucleus. However, the mechanism responsible for spatial proximity of specific loci is unknown. In this study, we use an 18 Mb region on 10q11.2-21 containing the RET gene and its recombination partners, the H4 and NCOA4 (ELE1) genes, as a model chromosomal region frequently involved in RET/PTC rearrangements in thyroid cancer. RET/PTC is particularly common in tumors from children exposed to ionizing radiation. Using fluorescence in situ hybridization and three-dimensional microscopy, the locations of five different loci in this region were mapped in interphase nuclei of normal human thyroid cells. We show that RET and NCOA4 are much closer to each other than expected based on their genomic separation. Modeling of chromosome folding in this region suggests the presence of chromosome coiling with coils of approximately 8 Mb in length, which positions the RET gene close to both, the NCOA4 and H4, loci. There was no significant variation in gene proximity between adult and pediatric thyroid cells. This study provides evidence for large-scale chromosome folding of the 10q11.2-21 region that offers a structural basis for nonrandom positioning and spatial proximity of potentially recombinogenic intrachromosomal loci.

Adolescent↗

PubMed2006

Effects of treated and untreated depressive symptoms on highly active antiretroviral therapy use in a US multi-site cohort of HIV-positive women.

This study examines the effects of treated and untreated depressive symptoms on the likelihood of utilization of highly active antiretroviral therapy (HAART) among a multi-site cohort of HIV-infected women who screened positive for probable depression. Data were collected biannually from 1996 through 2001 in a prospective cohort study. Random-effects regression analysis was used to estimate the longitudinal effects of mental health treatment on the probability of HAART utilization, controlling for clinical indicators (CD4 count, viral load), demographic features (race/ethnicity, income), and behavioural factors (recent crack, cocaine, or heroin use). Use of antidepressants plus mental health therapy, or use of mental health therapy alone significantly increased the probability of HAART utilization, compared to receiving no depression treatment. Use of antidepressants alone did not differ significantly from receiving no depression treatment. African American women and those who used crack, cocaine, or heroin also were less likely to use HAART. These findings suggest that efforts to enhance depressed women's access to psychopharmacologic treatment and therapy may increase their use of the most effective HIV therapies.

Adolescent↗

PubMed2004

Functional analysis of keratin components in the mouse hair follicle inner root sheath.

BACKGROUND: Recently, a family of novel type I keratins of the inner root sheath of the hair follicle were discovered, increasing the number of keratins known to be expressed in the hair follicle. The mouse database shows three keratins that are possible orthologues of these inner root sheath keratins. The sequences of these keratins include rather unusual changes to a highly conserved motif at the end of the alpha-helical rod domain of the proteins, thought to be important in filament assembly. OBJECTIVES: To investigate whether these keratins are expressed in the inner root sheath and to determine whether they assemble normally. METHODS: To investigate this, polyclonal antibodies were raised for immunolocalization of the keratins and their cDNAs were cloned for transfection into cultured cells. RESULTS: At least two of these keratins were expressed in the inner root sheath but the timing of expression of the different keratins was variable. Transfection of the relevant cDNAs into cells in culture indicated that these keratins were capable of integrating into existing keratin networks without disruption, but that de novo filament assembly with the type II inner root sheath keratin, mK6irs, was poor. CONCLUSIONS: These results provide further evidence of the complexity of keratin expression in the three concentric layers of the inner root sheath.

Animals↗

PubMed2004

Prevalence of human herpesvirus-8 salivary shedding in HIV increases with CD4 count.

Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), which occurs in epidemic form in human immunodeficiency virus(HIV)-infected individuals. Saliva is the only mucosal fluid in which infectious HHV-8 has been identified, although factors associated with HHV-8 salivary shedding remain unclear. Our study performed PCR analysis for HHV-8 DNA in saliva (and other body fluids) in 66 HIV- and HHV-8-co-infected women without KS so that we could examine predictors for HHV-8 DNA detection. CD4 count was the most significant predictor of HHV-8 salivary shedding, with increased prevalence of HHV-8 salivary DNA at higher CD4 counts. The odds of salivary HHV8 shedding at CD4 counts > = 350 cells/microL was 63 times the odds of shedding at CD4 < 350 (95%CI, 1.3-3078), with an increase in effect size when the analysis was restricted to those with a CD4 nadir > 200. Analysis of these data suggests an increased potential for HHV-8 transmission early in HIV infection, with implications for HHV-8 prevention.

Anti-HIV Agents↗

PubMed2001

Menetrier's disease.

An 8-year-old girl presented with persistent vomiting, pain abdomen and generalized edema. Barium studies and gastroscopy suggested hypertrophic gastropathy. Histopathological examination pointed the diagnosis towards Menetrier's Disease. There was spontaneous remission and the child required only supportive therapy.

Barium Sulfate↗

PubMed2001

Use of green fluorescent protein expressing Salmonella Stanley to investigate survival, spatial location, and control on alfalfa sprouts.

Laser scanning confocal microscopy (LSCM) was used to observe the interaction of Salmonella Stanley with alfalfa sprouts. The green fluorescent protein (gfp) gene was integrated into the chromosome of Salmonella Stanley for constitutive expression, thereby eliminating problems of plasmid stability and loss of signal. Alfalfa seeds were inoculated by immersion in a suspension of Salmonella Stanley (ca. 10(7) CFU/ml) for 5 min at 22 degrees C. Epifluorescence microscopy demonstrated the presence of target bacteria on the surface of sprouts. LSCM demonstrated bacteria present at a depth of 12 microm within intact sprout tissue. An initial population of ca. 10(4) CFU/g seed increased to 7.0 log CFU/g during a 24-h germination period and then decreased to 4.9 log CFU/g during a 144-h sprouting period. Populations of Salmonella Stanley on alfalfa seeds decreased from 5.2 to 4.1 log CFU/g and from 5.2 to 2.8 log CFU/g for seeds stored 60 days at 5 and 22 degrees C, respectively. The efficacy of 100, 200, 500, or 2,000 ppm chlorine in killing Salmonella Stanley associated with sprouts was determined. Treatment of sprouts in 2,000 ppm chlorine for 2 or 5 min caused a significant reduction in populations of Salmonella Stanley. Influence of storage on Salmonella Stanley populations was investigated by storing sprouts 4 days at 4 degrees C. The initial population (7.76 log CFU/g) of Salmonella Stanley on mature sprouts decreased (7.67 log CFU/g) only slightly. Cross-contamination during harvest was investigated by harvesting contaminated sprouts, then directly harvesting noncontaminated sprouts. This process resulted in the transfer of ca. 10(5) CFU/g Salmonella Stanley to the noncontaminated sprouts.

Bacterial Adhesion↗

PubMed2000

Difficulties in the prevention, diagnosis, and treatment of imported malaria.

BACKGROUND: Imported malaria is quite common in the United States. Increasing antimalarial drug resistance and changes in travel patterns may have important implications for the prevention, clinical presentation, and management of this disease. METHODS: Medical records were reviewed for 121 patients with microscopically confirmed malaria diagnosed at 2 university-affiliated hospitals in San Francisco, Calif, between 1988 and 1997. RESULTS: Among 57 travelers from the United States, only 13 (23%) had been compliant with an appropriate chemoprophylactic regimen. No patients developed falciparum malaria after consistent chemoprophylactic therapy with mefloquine hydrochloride. However, 12 (19%) of US residents with imported malaria developed Plasmodium vivax or Plasmodium ovale infections despite an appropriate chemoprophylactic regimen, generally with a late onset suggestive of relapsing disease. Clinical presentations were similar between foreign residents and American travelers and between patients with falciparum and nonfalciparum infections; 98% of patients had a history of fever. Sixteen percent of patients had received previous evaluations during which the diagnosis of malaria was not considered. In 9% of patients, there were errors in treatment. Only 1 patient developed severe malaria. CONCLUSIONS: Our results suggest that a standard chemoprophylactic regimen is highly effective in preventing falciparum malaria, but that many American travelers do not receive it. Also, relapsing P vivax or P ovale infection despite appropriate chemoprophylactic therapy was not uncommon among our cases. The presentation of imported malaria is nonspecific, highlighting the need to consider the diagnosis in any febrile patient who has been in a malaria-endemic area. Although errors in diagnosis and treatment were quite common in our study population, patient outcomes were good once the appropriate therapy was initiated.

Adolescent↗

PubMed2000

Phentolamine prevents the adverse effects of adenosine on glycolysis and mechanical function in isolated working rat hearts subjected to antecedent ischemia.

Adenosine inhibits glycolysis from exogenous glucose, reduces proton production and enhances post-ischemic left ventricular minute work (LV work) following ischemia in isolated working rat hearts perfused with glucose and fatty acids. In hearts partially depleted of glycogen by antecedent ischemic stress (AIS)--two cycles of ischemia (10 min) and reperfusion (5 min)--adenosine stimulates rather than inhibits glycolysis, increases proton production and worsens recovery of post-ischemic LV work. We determined if the switch in adenosine effect on glycolysis and recovery of LV work following ischemia in hearts subject to AIS was due to the reduction in glycogen content per se or because of alpha-adrenoceptor stimulation. One series of hearts underwent a 35-min period of substrate-free Langendorff perfusion (substrate-free glycogen depletion; SFGD) and a second series of hearts was subjected to AIS. Both series of hearts had a similar glycogen content (approximately 70 micromol/g dry wt) prior to drug treatment. In SFGD hearts perfused aerobically, adenosine (500 microM) inhibited glycolysis from exogenous glucose and reduced proton production. In SFGD hearts reperfused after prolonged ischemia, adenosine exerted similar effects on glucose metabolism and enhanced recovery of post-ischemic LV work (87.2 +/- 2.2% of preischemic values) relative to untreated hearts (25.9 +/- 13.3% of preischemic values). In AIS hearts perfused aerobically or subject to ischemia and reperfusion, phentolamine (1 microM) given in combination with adenosine, prevented adenosine-induced stimulation of glycolysis from exogenous glucose and reduced calculated proton production from glucose. Recoveries of post-ischemic LV work in AIS hearts for untreated, adenosine, phentolamine and adenosine/phentolamine groups were 34.4 +/- 11.4%, 8.6 +/- 3.9%, 16.3 +/- 13.5% and 73.2 +/- 13.1% respectively, of preischemic values. Glycogen depletion in the absence of ischemia does not switch the effect of adenosine from inhibition to stimulation of glycolysis or alter the cardioprotective properties of adenosine in hearts subject to ischemia and reperfusion. The detrimental switch in the metabolic and cardioprotective effects of adenosine, in hearts subject to AIS, can be prevented by phentolamine, an alpha-adrenoceptor antagonist. These data support the concept that modulation of glucose metabolism is an important factor in the mechanical functional recovery of the post-ischemic heart.

Adenosine↗

PubMed2000

A national Survey of Acute Myocardial Infarction and Ischaemia (SAMII) in the U.K.: characteristics, management and in-hospital outcome in women compared to men in patients under 70 years.

AIMS: To assess the clinical characteristics, management and outcome of women compared to men with acute myocardial infarction or ischaemia. DESIGN: A prospective clinical survey was made in a random sample of 94 District General Hospitals in the U.K. 1064 patients, <70 years of age, comprising six consecutive females and six consecutive males from each hospital, diagnosed on admission as acute coronary syndromes (myocardial infarction or myocardial ischaemia) were studied. Outcome measures included: admission and final diagnosis, time to delivery of care, inpatient management, complications and clinical outcome. RESULTS: Five hundred and three women and 561 men were admitted with a diagnosis of acute myocardial infarction or myocardial ischaemia. Women were older, waited longer between seeking and receiving advice, and much less likely to have infarction than men. After adjustment for age, diagnosis and past medical history there were no gender differences in initial and subsequent hospital management, in complications (recurrent ischaemia, arrhythmias, temporary pacing, heart failure), any routine procedure or outcome. Of all patients, 3.4% died in a District General Hospital, 12.2% were transferred to Specialist Cardiac Centres and 84.4% discharged home. Prophylactic medication on discharge was similar for men and women. CONCLUSION: After adjustment for age, diagnosis and past medical history, although women waited longer between seeking and receiving medical advice, in hospital their assessment, management, complications, outcome and follow-up arrangements were the same as for men. In hospital, management and outcomes were mainly influenced by age, diagnosis (infarction or ischaemia), a past history of coronary disease, but not by gender. This large, nationally representative, survey has found no evidence of important gender difference in the hospital management of acute ischaemic syndromes.

Adult↗

PubMed2000

Ventilatory pulmonary function tests in type 1 diabetes mellitus.

OBJECTIVE: To study the ventilatory pulmonary function tests (VPFT) in type one diabetes mellitus and to correlate it with duration, meticulous metabolic control and various complications of diabetes. METHODOLOGY: Spirometric evaluation of 50 young (15-30 years of age) type one diabetes mellitus patients was done under the case control longitudinal study. After recording baseline parameters patients were subjected to PFT. OBSERVATIONS: Degree of derangement in VPFTs was directly related to duration and metabolic control of diabetes. VPFT parameters such as FVC, FEV1, PEFR, MEF 75% and MEF 25% showed significant reduction (p = 0.009, = 0.001, = 0.001, = 0.05 respectively). Similarly patients with HbA1c > 10% showed significant reduction in FVC, FEV1, PEFR and MEF 75% (p = 0.001 for each). Diabetic patients with complications particularly peripheral neuropathy and nephropathy had significant reduction in FVC, FEV1 and PEFR (p = 0.001). CONCLUSION: Spirometric evaluation in type one diabetes mellitus showed varying derangements in the different parameters of VPFTs, suggestive of dominantly restrictive with some obstructive pattern as indicated by significant decline in FVC, PEFR and MEF 75%.

Adolescent↗

PubMed1999

Deficiency in myocardial NO biosignalling after cardioplegic arrest: mechanisms and contribution to post-storage mechanical dysfunction.

1 In order to understand mechanisms that limit the safe ischaemic time of donor hearts, this study evaluated NO/cyclic GMP biosignalling in the recovery of function after cardioplegia and hypothermic storage. 2 Hearts removed from anaesthetized rats were either perfused in working mode (Fresh) or arrested (St. Thomas' II cardioplegia) and stored at 3 degrees C for 8 h (CPL) prior to working mode perfusion. LV work and indices of the production of NO (Ca2+-dependent and Ca2+-independent NOS), cyclic GMP (soluble guanylyl cyclase (sGC) and GTP) and superoxide (xanthine oxidase (XO) and xanthine dehydrogenase (XDH)) were measured. 3 Relative to Fresh hearts, CPL hearts were deficient in cyclic GMP and had poor function. Correction of cyclic GMP deficiency (SNP, 200 microM) improved LV work and LV compliance. SNP effects were prevented by inhibition of sGC (ODQ, 3 microM), and potentiated by inhibition of cyclic GMP-dependent phosphodiesterase (zaprinast, 20 microM). SNP (200 microM) had no effect on function of Fresh hearts. 4 NOS activities (pH = 7.2) were similar in CPL and Fresh hearts, but at end-ischaemic pH (6.3), Ca2+-dependent NOS activity was reduced. The sensitivity of sGC to SNP was greater, and activities of XO and XDH were higher, in CPL than in Fresh hearts. 5 The deficiency in NO biosignalling in CPL hearts may arise due to acidosis-induced inhibition of NOS activity, reduced availability of GTP and/or enhanced inactivation of NO by superoxide. These findings provide rationales for novel strategies to prevent the deficiency in NO biosignalling and so improve the function of the transplanted heart.

Adenosine Triphosphate↗

PubMed1999

A comparison of CD34+ cell selected and unselected autologous peripheral blood stem cell transplantation for multiple myeloma: a case controlled analysis.

Following ASCT for multiple myeloma, it is unclear whether relapse is due solely to the presence of residual myeloma cells after myeloablation, or whether it is in part attributable to contamination of the stem cell harvest with viable malignant cells. Positive selection of CD34+ cells markedly reduces plasma cell contamination. We performed a case controlled analysis in which 15 patients with myeloma who underwent autologous PBSCT with CD34+cell selection using the Ceprate System (index group), were compared with 15 matched controls. All subjects received an identical preparative regimen. The median times to neutrophils >/=0.5 x 10(9)/l and unsupported platelets >/=50 x 10(9)/l were 14 and 23 days for the CD34+cell selected group and 11 (P = 0.03) and 14 (P = 0.029) for the case controls. Median follow-up of purged patients from autologous PBSCT was 32 months (range 18-43). At 36 months, the probability of PFS was 47 +/- 14% and 46 +/- 14% in the index and control groups (P = 0.44). The 3 year probability of OS was 69 +/- 13% for the CD34+ cell selected arm and 66 +/- 12.4% in unpurged patients (P = 0.91). Median PFS for the cell selected group is 24 months (CI 19.1-36.0), and 29 months for controls (CI 7.1-50.9). Eleven patients undergoing cell selection remain alive, seven of whom are progression free. At the same time-point after unpurged autologous PBSCT, the corresponding figures are 12 patients alive, with seven remaining progression free. Autologous PBSCT with CD34+ cell selection is both feasible and safe, but results in delayed engraftment as compared to case controls. The 3 year probability of PFS and OS in the cell selected arm was similar to that of the unpurged controls. Our findings indicate that autologous PBSCT with CD34+ cell selection appears not to have any favourable effect on disease progression. However, the results of this case controlled analysis should be cautiously interpreted, and the role of CD34+ selection in autologous PBSCT should be further investigated by large randomised trials.

Adult↗

PubMed1999

Can CT pulmonary angiography replace ventilation-perfusion scans as a first line investigation for pulmonary emboli?

A prospective study was performed to determine efficacy of diagnosis of pulmonary emboli by computed tomographic pulmonary angiography (CTPA) in patients who underwent both CTPA and ventilation-perfusion (V/Q) scanning. The results were compared with the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study in which conventional pulmonary angiography had been performed instead of CTPA. Forty-two of 161 (26%) patients had a positive CTPA compared with a 27% prevalence in the PIOPED population. Fourteen of 16 patients (87.5%) with high-probability V/Q scans also had a positive CTPA compared with 87% in PIOPED. Twelve of 40 patients (30%) with intermediate probability V/Q scans also had a positive CTPA compared with 34.7% in PIOPED, while 12 of 80 patients (15%) who had low-probability V/Q scans had positive CTPA compared with 14.5% in PIOPED. Four of 25 patients (16%) with normal V/Q scans had positive CTPA compared with 0% in PIOPED. While the present study size was relatively small, the results compared favourably with PIOPED, suggesting that equivalent prevalence of clot was being detected using CTPA. This result, together with the cost considerations, has led us to replace V/Q scanning with CTPA for investigation of the majority of cases of suspected, acute pulmonary emboli.

Angiography↗

PubMed1999

Effects of eprosartan on glomerular injury in rats with reduced renal mass.

The effects of the selective angiotensin AT1 receptor antagonist, eprosartan, were evaluated in experimental renal disease. Five-sixth nephrectomy in male Munich-Wistar rats led to the development of hypertension, proteinuria and remnant glomerulosclerosis. Administration of the AT1 receptor antagonist, eprosartan, for 4 weeks resulted in inhibition of angiotensin II activity as confirmed by a reduced blood pressure response to exogenous angiotensin II challenge. Compared to vehicle treatment, eprosartan normalized blood pressure, reduced proteinuria and limited remnant glomerulosclerosis. These data suggest that eprosartan may provide a new tool in the treatment of progressive renal disease.

Acrylates↗

PubMed1998

Cardioprotection by activation of NO/cGMP pathway after cardioplegic arrest and 8-hour storage.

BACKGROUND: We determined whether activation of the nitric oxide/cyclic guanosine monophosphate pathway by sodium nitroprusside (SNP) protects hearts subjected to cardioplegic arrest and prolonged hypothermic storage. METHODS: Isolated rat hearts arrested with St. Thomas' II cardioplegia and stored at 3 degrees +/- 1 degree C for 8 hours were reperfused at 37 degrees C in Langendorff (10 minutes) and working (60 minutes) modes. RESULTS: During reperfusion, left ventricular work was depressed in stored hearts relative to fresh hearts. When present during arrest, storage, and both reperfusion phases, SNP (200 mumol/L) improved work to values close to those in fresh hearts. When added only during the 10-minute period of Langendorff reperfusion, SNP also improved the subsequent recovery of work. This effect was antagonized by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Poststorage coronary perfusion was not increased by SNP. CONCLUSIONS: The ability of SNP to enhance recovery independent of changes in coronary perfusion and in an ODQ-sensitive manner suggests that SNP-induced protection is due to activation of the myocardial nitric oxide/cyclic guanisine monophosphate pathway. These results suggest that supplementing cardioplegic solutions with SNP, administering SNP during early reperfusion, or both may offer additional means to improve donor heart preservation.

Animals↗

PubMed1998

Establishing an ultrasound guided peripherally inserted central catheter (PICC) insertion service.

Peripherally inserted central catheters (PICCs) are an increasingly used means of medium to long-term intravenous access. We have established an ultrasound (US) guided PICC insertion service at our institution that has largely replaced blind bedside insertions. One hundred and six PICCs were inserted in the upper arms of 89 patients, over a 6-month period with a 100% success rate. The technique for US guided vein puncture and guidewire insertion is described. Catheter related complications included infection (6 proven cases; 3.1 infections per 1000 catheter days); catheter blockage (7), breakage (8) and unintentional removal (5). Catheter blockage, breakage and partial unintentional removal are potentially remediable complications using guide-wire techniques under fluoroscopic guidance. The management of catheter related infection is discussed. We have encouraged early communication with our clinical colleagues in order to facilitate the management of such complications and minimize unnecessary catheter removal.

Catheterization, Central Venous↗

PubMed1998

Contribution of tubular injury to loss of remnant kidney function.

BACKGROUND: The remnant kidney model has been widely used to identify mechanisms responsible for the progression of renal disease. However, the structural changes associated with progressive loss of function in this model have not been well characterized. METHODS: Kidney function and structure were assessed at 10 weeks (REM 10) and 25 weeks (REM 25) after five-sixths renal ablation and in control rats (Control). Serial sections were examined to relate glomerular and tubular structure in individual nephrons. RESULTS: Remnant kidney function declined between 10 and 25 weeks after ablation (GFR 0.90 +/- 0.34 vs. 0.23 +/- 0.07 ml/min, REM 10 vs. REM 25, P < 0.05). This decline in function was associated with an increase in the prevalence of globally sclerotic glomeruli (14 +/- 10 vs. 0 +/- 0 vs. 0 +/- 0%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM 10 and Control). The decline in remnant kidney function between 10 and 25 weeks was also associated with the appearance of glomeruli that were atubular (48 +/- 14 vs. 9 +/- 8 vs. 3 +/- 5%, REM 25 vs. REM 10 vs. Control, P < 0.05 REM 25 vs. REM 10 and Control) or connected to atrophic proximal tubule segments (26 +/- 10 vs. 11 +/- 6 vs. 1 +/- 2%, REM 25 vs. REM 10 vs. Control, P < 0.05 all comparisons). Atubular glomeruli, which usually had open capillary loops available for filtration, were more numerous than globally sclerotic glomeruli at 25 weeks after ablation. CONCLUSIONS: These findings indicate that tubular injury contributes to progressive loss of renal function following reduction in nephron number.

Animals↗

PubMed1996

Inhibition of glycolysis and enhanced mechanical function of working rat hearts as a result of adenosine A1 receptor stimulation during reperfusion following ischaemia.

1. This study examined effects of adenosine and selective adenosine A1 and A2 receptor agonists on glucose metabolism in rat isolated working hearts perfused under aerobic conditions and during reperfusion after 35 min of global no-flow ischaemia. 2. Hearts were perfused with a modified Krebs-Henseleit buffer containing 1.25 mM Ca2+, 11 mM glucose, 1.2 mM palmitate and insulin (100 muu ml-1), and paced at 280 beats min-1. Rates of glycolysis and glucose oxidation were measured from the quantitative production of 3H2O and 14CO2, respectively, from [5-3H/U-14C]-glucose. 3. Under aerobic conditions, adenosine (100 microM) and the adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA, 0.05 microM), inhibited glycolysis but had no effect on either glucose oxidation or mechanical function (as assessed by heart rate systolic pressure product). The improved coupling of glycolysis to glucose oxidation reduced the calculated rate of proton production from glucose metabolism. The adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 0.3 microM) did not alter glycolysis or glucose oxidation per se but completely antagonized the adenosine- and CHA-induced inhibition of glycolysis and proton production. 4. During aerobic reperfusion following ischaemia, CHA (0.05 microM) again inhibited glycolysis and proton production from glucose metabolism and had no effect on glucose oxidation. CHA also significantly enhanced the recovery of mechanical function. In contrast, the selective adenosine A2a receptor agonist, CGS-21680 (1.0 microM), exerted no metabolic or mechanical effects. Similar profiles of action were seen if these agonists were present during ischaemia and throughout reperfusion or when they were present only during reperfusion. 5. DPCPX (0.3 microM), added at reperfusion, antagonized the CHA-induced improvement in mechanical function. It also significantly depressed the recovery of mechanical function per se during reperfusion. Both the metabolic and mechanical effects of adenosine (100 microM) were antagonized by the nonselective A1/A2 antagonist, 8-sulphophenyltheophylline (100 microM). 6. These data demonstrate that inhibition of glycolysis and improved recovery of mechanical function during reperfusion of rat isolated hearts are mediated by an adenosine A1 receptor mechanism. Improved coupling of glycolysis and glucose oxidation during reperfusion may contribute to the enhanced recovery of mechanical function by decreasing proton production from glucose metabolism and the potential for intracellular Ca2+ accumulation, which if not corrected leads to mechanical dysfunction of the postischaemic myocardium.

Adenosine↗