PubMed Health⌕ Search

Biomedical subjects

S Offenbacher

Publications and source records attributed to S Offenbacher.

At least 73 records · Page 4Linked to original sources
PubMed1996

Clinical/biological outcomes of treatment for pericoronitis.

PURPOSE: This prospective clinical study was designed to determine the clinical and biologic outcomes of treatment for minor signs and symptoms of pericoronitis. PATIENTS AND METHODS: Patients (n = 20) with all third molars, presenting consecutively to an academic clinical center for treatment of minor signs and symptoms of pericoronitis, were enrolled in the study. At the initial visit, gingival crevicular fluid (GCF) samples to assess levels of the cytokines interleukin- 1b (IL-1b) IL-1b and prostaglandin E2 (PGE2) as a measure of the host inflammatory response, and plaque samples to identify microorganisms, were collected from the distal of all second molars and the mesial of first molars. Standardized vertical bite wing radiographs were taken to assess alveolar bone height on the distal of the second molars and the inclination and the degree of eruption of the third molar. Full-mouth periodontal probing was conducted to determine probing depths and relative clinical attachment levels (CAL). Pain levels were assessed with Gracely verbal descriptor scales for sensory intensity and unpleasantness and 10-cm visual analog scales. Symptomatic third molar sites were treated with local debridement and irrigation after baseline data collection. One week after entry, data were collected again. Subsequently, the patients were scheduled for removal of all third molars. Data collection was repeated 3 months postsurgery. As controls, data were collected from 12 subjects who had asymptomatic third molars removed previously. RESULTS: At entry, symptomatic mandibular third molars (n = 21) were mostly vertical (n = 18) and at or above the occlusal plane (n = 19). No maxillary teeth had symptoms. Microbial counts were elevated for specific anaerobic microorganisms. GCF IL-1b levels were elevated at the distal of second molars adjacent to symptomatic third molars, as compared with asymptomatic third molars and second molars in control patients. Alveolar bone levels and CAL on the distal of second molars were normal. At 1 week, patients' pain symptoms and IL-1b levels were reduced, but microbial counts remained high. Three months after surgery, patients had no pain symptoms, and alveolar bone levels and CAL were similar to entry levels. IL-1b levels were elevated at both the distal of second molars and the mesial of first molars for all patients; microbial counts decreased, although not to levels of control patients. No increase in microbial counts for Porphyromonas gingivalis or Bacteroides forsythus, or GCF PGE2 levels, risk factors for progressive periodontal disease, was detected in samples taken from the study patients. CONCLUSION: Pericoronitis expressed by minor signs/symptoms in these patients was associated with considerable discomfort. Symptomatic mandibular third molars were vertical and at or near the occlusal plane. Additionally, this condition was characterized by microbial flora and GCF inflammatory mediator levels that are more consistent with gingivitis than periodontitis. Removal of third molars eliminated symptoms, but the microbial burden and an affected patient's inflammatory response, as measured by IL-1b levels, remained elevated as compared with controls. Further study is needed to determine which of these factors can be used to identify patients at risk for pericoronitis before symptoms arise.

Adolescent↗
PubMed1996

Evaluation of ketorolac concentrations in plasma and gingival crevicular fluid following topical treatment with oral rinses and dentifrices.

Two clinical studies were conducted to determine the relative amounts of ketorolac detectable locally in the gingival crevicular fluid (GCF) and systemically in plasma after oral, topical drug administration. The rinse study compared topical administration of three concentrations of ketorolac tromethamine (0.1%, 0.5%, and 0.01%) in oral rinse formulations administered topically and a perorally administered capsule (10 mg), and the dentifrice study compared two concentrations of ketorolac in dentifrice formulations (0.15% and 1.0%) with a 0.1% oral rinse, all treatments administered topically. The dose-corrected systemic availability of the three oral rinses evaluated in the rinse study relative to the peroral capsule was about 15%. However, the ratios of the observed maximum GCF ketorolac concentration to maximum plasma ketorolac concentration ranged from 22 to 49, compared to less than 1 for the peroral ketorolac capsule. Using this ratio as an estimate of the ability of a treatment to target the drug to the gingival tissue, these data indicate that the ketorolac oral rinses achieved greater delivery of drug to the gingival tissue (presumed site of action for periodontitis) with a lower systemic drug load than peroral administration of a ketorolac capsule. The dose-corrected relative systemic bioavailabilities for the dentifrice treatments with respect to the 0.1% rinse in the dentifrice study were 59.2% and 86.4% for the 1.0% and 0.15% dentifrices, respectively, indicating that significantly less ketorolac was systemically available from the two dentifrices relative to the oral rinse. The relative bioavailabilities of ketorolac in the GCF after dosing with the dentifrice formulations with respect to the rinse were 89.1% for the 1.0% dentifrice and 19.7% for the 0.15% dentifrice. Thus, the 1.0% dentifrice appears to provide statistically equivalent levels of ketorolac to the gingival tissue as the 0.1% oral rinse with significantly less systemic exposure. The T1/2 of ketorolac in the GCF was about 0.5 h for all three treatments, which is significantly less than the plasma half-life of about 5.3 h. These data suggest that GCF levels of ketorolac should remain above the IC50 for PGE2-stimulated IL-1 bone resorption for about 7 h following treatment, assuming continuation of the first-order elimination observed over the first two postdosing hours. We conclude that oral rinses and dentifrices are effective and preferred vehicles for administration of ketorolac for use in treatment of periodontitis.

Administration, Topical↗
PubMed1996

The effect of ketoprofen creams on periodontal disease in rhesus monkeys.

Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The biochemical data demonstrated early and significant suppression of GCF-LTB4 by both ketoprofen formulations at 1 month, which preceded the significant suppression of GCF-PGE2 at 2 and 3 months in the ligature model (p < 0.003) and at 2 to 6 months in the spontaneous model (p < 0.02). We conclude that ketoprofen at 1% level in suitable topical vehicles can effectively inhibit GCF-LTB4 and GCF-PGE2 and positively alter alveolar bone activity in the ligature-induced model of periodontitis in the monkey.

Administration, Topical↗
PubMed1996

Exploratory case-control analysis of psychosocial factors and adult periodontitis.

We explored the association between social factors and adult periodontitis by comparing self-reported information for daily strains and symptoms of depression in 71 cases and 77 controls. Cases and controls were selected from among 1,426 participants in the Erie County Risk Factor Study. We found differences among those who scored higher than their peers on measures of social strain. The odds ratio (OR) and 95% confidence interval (95% CI) for the association between case status and Role Strain score of 2.27 or more was 2.84, 95% CI = 1.08 to 7.46. We also examined serum antibody, dichotomized at the median, for three periodontal pathogens (Bacteroides forsythus [IgG Bf], Porphyromonas gingivalis [IgG Pg], Actinobacillus actinomycetemcomitans [IgG Aa]), and assessed interaction between antibody levels and a Depression score derived from the Brief Symptom Inventory. IgG Pg and IgG Aa were both strongly associated with case status (OR = 4.52, 95% CI = 1.99 to 10.3 and OR = 5.29, 95% CI = 2.34 to 12.0, respectively). IgG Bf was associated with periodontal disease but only among individuals who had higher scores for Depression (OR = 6.75, 95% CI = 1.25 to 36.5). Smoking status was associated with case status (OR = 4.95, 95% CI = 1.86 to 13.2). We assessed these findings prospectively by examining factors associated with more extensive disease among the 71 case subjects after 1 year of follow-up. We found baseline smoking status and IgG Bf among individuals scoring high on Depression at baseline to be associated with more extensive disease (8.1% or more of the sites showing further breakdown). In this population an elevated Depression score may be a marker for social isolation, which could play a role in immune function during periods of social strain. This exploratory analysis has served to identify specific lines of inquiry concerning psychosocial measures as important environmental factors in adult periodontitis.

Adult↗
PubMed1996

Periodontal infection as a possible risk factor for preterm low birth weight.

Peridontal diseases are gram-negative anaerobic infections that can occur in women of childbearing age (18 to 34 years). In the present investigation we sought to determine whether the prevalence of maternal periodontal infection could be associated with preterm low birth weight (PLBW), controlling for known risk factors and potential covariates. A case-control study of 124 pregnant or postpartum mothers was performed. PLBW cases were defined as a mother with a birth of less than 2,500 g and one or more of the following: gestational age < 37 weeks, preterm labor (PTL), or premature rupture of membranes (PROM). Controls were normal birth weight infants (NBW). Assessments included a broad range of known obstetric risk factors, such as tobacco use, drug use, alcohol consumption, level of prenatal care, parity, genitourinary infections, and nutrition. Each subject received a periodontal examination to determine clinical attachment level. PLBW cases and primiparous PLBW cases (n = 93) had significantly worse periodontal disease than the respective NBW controls. Multivariate logistic regression models, controlling for other risk factors and covariates, demonstrated that periodontal disease is a statistically significant risk factor for PLBW with adjusted odds ratios of 7.9 and 7.5 for all PLBW cases and primiparous PLBW cases, respectively. These data indicate that periodontal diseases represent a previously unrecognized and clinically significant risk factor for preterm low birth weight as a consequence of either PTL or preterm PROM.

Adolescent↗
PubMed1996

Periodontal disease and cardiovascular disease.

It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.

Alveolar Bone Loss↗
PubMed1995

Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet: influence of cyclooxygenase inhibition.

Tumor necrosis factor-alpha (TNF) is believed to play an important role in mediating many of the pathophysiologic changes accompanying bacterial sepsis. In order to characterize the cardiopulmonary responses to TNF in a young animal model and to determine to what extent these changes were secondary to cyclooxygenase byproducts, three groups of mechanically ventilated piglets received an infusion of either TNF, indomethacin followed by TNF (Indo+TNF) or neither (control). Compared to controls at 120 min, TNF resulted in the following changes beginning 30-60 min after the infusion began: mean pulmonary artery pressure (Ppa) increased from 1.7 +/- 0.3 to 4.4 +/- 0.7 kPa (13 +/- 2 to 33 +/- 5 mm Hg) (p < 0.001); cardiac output (CO) fell from 0.28 +/- 0.05 to 0.20 +/- 0.07 liters/kg/min (p < 0.01); mean arterial blood pressure (Psa) decreased from 9.5 +/- 1.2 to 7.9 +/- 1.9 kPa (71 +/- 9 to 59 +/- 14 mm Hg) as did pH from 7.49 +/- 0.04 to 7.13 +/- 0.17 (p < 0.001). Dynamic lung compliance (Cdyn) also decreased; however, pulmonary resistance (RI) remained unchanged. Thromboxane B2 (TxB2) rose in all animals at 60 min coincident with Psa elevation and was significantly blocked by Indo (p < 0.03). In the Indo+TNF group the early TNF-induced rise in Psa was blunted compared to the TNF group [2.9 +/- 1.2 vs. 3.6 +/- 0.8 kPa (22 +/- 3 vs. 27 +/- 6 mm Hg; p < 0.04)] as were the late decreases in pH and Psa (p < 0.04). There were no significant changes in Cdyn secondary to Indo. Although delayed, the hemodynamic changes observed with TNF infusion are similar to those reported for piglets receiving group B streptococci; however, in contrast to the latter the early changes secondary to TNF are only mildly effected by indomethacin. The significant improvement in the late occurring hypotension and acidosis suggests that TNF may act in part via the cyclooxygenase pathway as a mediator of the late hypotension associated with sepsis.

Animals↗
PubMed1994

Effects of a Porphyromonas gingivalis infection on inflammatory mediator response and pregnancy outcome in hamsters.

This study examines the effects of various localized, nondissemination challenges of Porphyromonas gingivalis on inflammatory mediator production and pregnancy outcome in the golden hamster. Live or heat-killed (HK) organisms were inoculated into a previously implanted subcutaneous tissue chamber on the 8th day of gestation to determine the effects on fetal weight, viability, and resorption. In one group of animals, HK organisms were inoculated prior to mating to determine the effects of previous exposure on day-8 gestational challenges. Chamber contents were assayed at 1 and 5 days after challenge for prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF-alpha). All P. gingivalis challenges caused a significant increase in chamber PGE2 and TNF-alpha at P < 0.01 in the following order of potency: HK < Live < HK+Live. For example, following the HK+Live challenge, PGE2 levels increased from 4.7 pg/ml at baseline to 362 pg/ml at day 5 and TNF-alpha increased from 26.4 pg/ml to 724 pg/ml at day 5. The same order of potency of the various challenges was maintained with regard to the toxic effects of P. gingivalis on pregnancy outcome. For the HK+Live challenge, fetal weight was decreased 24%; embryolethality increased to 26.5% and the percent fetal resorption increased to 10.6% compared with control animal levels. There was a statistically significant association between increasing levels of both PGE2 and TNF-alpha and fetal growth retardation and embryolethality at P < 0.001. These data suggest that infections with gram-negative periodontal pathogens can elicit adverse pregnancy outcomes and that the levels of PGE2 and TNF-alpha produced as a result of challenge are associated with the severity of fetal effect.

Animals↗
PubMed1994

Effects of Escherichia coli and Porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster.

This report describes the effects of two gram-negative bacterial endotoxin (lipopolysaccharide [LPS]) preparations on hamster pregnancy outcome variables. Single intravenous challenges with Escherichia coli and Porphyromonas gingivalis LPS on day 8 of pregnancy produced dose-dependent effects on fetal weight malformation and fetal resorption with E. coli LPS having potent embryolethal effects. Premating maternal exposure to P. gingivalis produced embryolethal effects similar to those of E. coli. These data suggest that maternal exposure to P. gingivalis LPS prior to and during pregnancy can induce deleterious effects on the developing fetus.

Abnormalities, Drug-Induced↗
PubMed1994

The secretion of PGE2, IL-1 beta, IL-6, and TNF alpha by adherent mononuclear cells from early onset periodontitis patients.

The secretion of prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) by adherent mononuclear cells (AMNC) from 28 patients with early-onset periodontitis was studied. The early onset-periodontitis patients consisted of 12 patients with localized juvenile periodontitis (LJP) and 16 patients with severe generalized periodontitis (SGP). The AMNC responses to different concentrations of lipopolysaccharide (LPS) (E. coli) were determined in these 28 patients and compared to 14 healthy controls. Mediator levels in the supernatant were measured using radioimmunoassays for PGE2, IL-1 beta, and IL-6 determination and an enzyme linked immunosorbent assay for TNF alpha levels. The mean age of the patients was 19.9 years for the LJP group, 30.4 years for SGP, and 28.0 years for the controls. The mean number of teeth per patient with attachment loss of > 6 mm was 4.75 in the LJP patients and 17.3 in the SGP group. In the absence of LPS, LJP AMNC secreted significantly more PGE2 than unstimulated control or SGP AMNC, while similar baseline amounts of IL-1 beta, IL-6, and TNF alpha were secreted by AMNC from the 3 patient groups. LPS stimulation resulted in the dose-dependent secretion of significantly higher levels of PGE2 by LJP AMNC compared to SGP AMNC which in turn secreted significantly more than controls. TNF alpha secretion by LJP monocytes was significantly greater than the SGP and the control groups while IL-1 beta secretion by the SGP AMNC was depressed compared to the other two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Attachment loss trends over 3 years in community-dwelling older adults.

Most of our knowledge regarding the natural history of periodontitis in adults has come from clinical studies of dental patients. However, it is known that dental patients usually are not representative of what actually happens in the population. For this type of information, epidemiologic studies are required. The purpose of this paper is to present the trends in attachment loss over a 3-year period in a population of community-dwelling elderly blacks and whites. Specifically, this paper presents attachment loss trends both at the person and site level to address the following issues: 1) whether attachment loss during one period in time makes a person at higher risk for attachment loss at a subsequent period; 2) whether sites with deeper periodontal pockets at baseline are more likely to experience future attachment loss; and 3) whether teeth that experience attachment loss during one time period are more likely to be lost at the next time period. In 1988, the University of North Carolina School of Dentistry initiated the Piedmont 65+ Dental Study, which is a subsample of the parent study, the Piedmont 65+ Study of the Elderly under the direction of investigators from Duke University. The dental study subsample was designed to elicit 800 dentate respondents in the 5-county area who were examined again at 18 and 36 months. Our findings indicated that, for the two 18-month periods investigated, attachment loss during the first period was related positively to the incidence of attachment loss at a subsequent period at the person level, but not at the site level.(ABSTRACT TRUNCATED AT 250 WORDS)

Black or African American↗
PubMed1993

Flurbiprofen in the prevention and treatment of experimental gingivitis.

A clinical trial was undertaken to examine the effects of a potent cyclooxygenase inhibitor, flurbiprofen, on both developing and established gingivitis in humans. 21 subjects with healthy gingiva abstained from all oral hygiene procedures for 21 days. 7 subjects were prescribed flurbiprofen, 50 mg b.d. beginning from baseline and a control group (Cl, n = 14) were given placebo. Gingival redness and bleeding on probing were assessed at baseline, 7, 14 and 21 days. Crevicular fluid (GCF) samples were also taken to determine concentrations of PGE2, TxB2 and LTB4 at baseline and at 21 days. Results show that flurbiprofen significantly inhibited the development of redness and bleeding (p < 0.001) effects which were associated with a significant inhibition of TxB2 (p < 0.05). There were no apparent flurbiprofen effects on GCF-PGE2 or GCF-LTB4 during this 21-day gingivitis, model To assess the effects of flurbiprofen on established experimental gingivitis, the model was extended to 28 days. On day 21, the Cl group was subdivided into 2 groups of 7 subjects. One group was prescribed flurbiprofen (50 mg b.d.) for 7 days and controls (C2) continued to take placebo. All subjects continued to abstain from tooth cleaning. Pretreatment (day 21) and post-treatment (day 28) comparisons showed that flurbiprofen again significantly inhibited bleeding (p < 0.001), but did not affect redness. Control subjects demonstrated a significant elevation in gingival bleeding on day 28, and this was associated with significant rises in GCF-PGE2 (p < 0.001), GCF-TxB2 (p < 0.01) and GCF-LTB4 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Changes in crevicular fluid levels of interleukin-1 beta, leukotriene B4, prostaglandin E2, thromboxane B2 and tumour necrosis factor alpha in experimental gingivitis in humans.

We conducted a study to determine the sequence of cytokine and lipid mediator activation within the periodontium during the development of experimental gingivitis in humans. Crevicular fluid samples were collected from 7 previously cleaned, healthy patients at baseline, 1, 2, 3 and 4 weeks following the cessation of all oral hygiene measures. Gingival and plaque scores were taken at each visit to follow the development of gingivitis and plaque retention. Crevicular fluid samples were assayed in quadruplicate for prostaglandin E2 (PGE2), thromboxane B2 (TxB2), leukotriene B4, interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) by RIAs or ELISAs, maintaining site pairing to examine temporal changes. Redness scores (expressed as mean percentage of sites with redness present) increased almost linearly from a baseline value of zero to approximately 40% at 1 week, 59% at 2 weeks, 83% at 3 weeks and 100% at 4 weeks. The mean % of sites with bleeding on probing increased gradually from zero at baseline to 5% at 3 weeks and then rose abruptly to 25% at 4 weeks. CF-PGE2 and CF-TxB2 levels remained fairly stable at baseline levels for the first 3 weeks then rose sharply by 2.5- and 2-fold, respectively, at 4 weeks. CF-LTB4 levels increased 2-fold by 1 week and 4-fold by 4 weeks. The CF levels of IL-1 beta increased abruptly from mean baseline values of 16.5 +/- 9.3 ng/ml to 131 +/- 76.0 ng/ml at 1 week and remained at this level for the duration of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

New clinical diagnostic strategies based on pathogenesis of disease.

The pathogenesis of periodontal tissue destruction involves the orchestrated sequential activation of several components of the host response, each of which have the potential for providing diagnostic information regarding the health or disease status of the periodontium. These events include the bacterial triggering of serum components, the release of vasoactive compounds, the recruitment of inflammatory cells, the activation of phagocytes, the local secretion of immunoglobulins and inflammatory mediators, as well as connective tissue remodeling. For purposes of diagnosis, much attention has been directed toward the measurement of local levels of specific byproducts of the pathogenic process either within the tissues or in the adjacent crevicular fluid. These are site-directed assessments of the local concentration of these byproducts, and with the important exception of antibody levels, very few byproducts of the periodontal pathogenic process have been studied on a systemic level. However, since the risk associated with periodontal disease progression is primarily patient-based and secondarily site-based, there is an increasing need to identify patients at risk for intervention strategies. Furthermore, there are substantial data that periodontal diseases are specific infections that occur in an appropriately susceptible host. The expression of periodontal disease has a strong genetic component, which presumably defines the host's response thereby affecting susceptibility. For this reason, there is increased interest in defining those elements of the host response which result in susceptibility to disease. The ultimate objective of a diagnostic strategy is to identify patients who are potentially at risk for acquiring disease to enable preventive measures.

Antibodies, Bacterial↗
PubMed1993

Adenosine regulates coronary blood flow during increased work and decreased supply.

Adenosine may mediate coronary vasodilation during work-related hyperemia and during ischemia. We tested whether adenosine blockade with 8-p-sulfophenyltheophylline (PSPT) prevented dobutamine-induced hyperemia or magnified the reductions in flow due to vasopressin. Control (n = 8) and test (n = 7) dogs received paired infusions of dobutamine (70 micrograms/min iv for 5 min). Test dogs received PSPT (10 mg/kg iv) between doses. In both groups, paired infusions elicited comparable increases in oxygen consumption. However, in test dogs, the hyperemia was reduced significantly. Thus adenosine mediates the hyperemia of dobutamine. Separately, control dogs (n = 9) received vasopressin (0.6 microgram ic over 5 min); test dogs (n = 7) received PSPT before vasopressin. Vasopressin maximally increased coronary resistance by 3 min; effects were gone by 10 min. With PSPT, coronary resistance was increased further and remained high beyond 10 min. Thus adenosine-mediated vasodilation moderates the severity and duration of ischemia. These results indicate the importance of adenosine in mediating coronary flow during increased demand and reduced supply.

Adenosine↗