Impact of early versus delayed umbilical cord clamping on term neonates' haemoglobin levels: a randomized controlled trial.

OBJECTIVE: To compare the effects of early and delayed cord clamping on the haemoglobin levels of neonates delivered at term. METHODS: This randomized controlled trial enrolled pregnant women during the second stage of labour. They were randomized into either the early cord clamping (ECC) group or the delayed cord clamping (DCC) group in the ratio of 1:1. Following delivery of the baby, the umbilical cords of participants in the ECC group were clamped within 30 s of delivery of the neonate while those of participants in the DCC group were clamped after 2 min from the delivery of the neonate. The primary outcome measure was the effect of ECC and DCC on the haemoglobin levels of neonates delivered at term. RESULTS: A total of 270 pregnant women were enrolled in the study. Their baseline sociodemographic and clinical characteristics were similar in both groups. There was no significant difference in the mean haemoglobin level between ECC and DCC groups at birth. The mean haemoglobin level of the neonates at 48 h postpartum was significantly higher in the DCC group than the ECC group. CONCLUSION: DCC at birth was associated with a significant increase in neonatal haemoglobin levels at 48 h postpartum when compared with ECC.Trial Registration: The trial was registered at Pan African Clinical Trial Registry with approval number PACTR202206735622089.

Phylogenetic variants of Mycoplasma hominis from pregnant women and women presenting with infertility in Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria

Background: Much controversies have been associated with the pathogenicity of Mycoplasma hominis but little has been done to unravel the mystery behind the different views. This study aimed at investigating the genetic variants abounding within M. hominis and the distribution of the virulent genes among the variants. Methodology: Twenty (20) M. hominis isolates from high vaginal swabs of women (11 from pregnant women and 9 from women presenting with infertility) attending the Obstetrics and Gynaecology clinics of Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria, were sequenced using 16S rRNA universal gene target for the purpose of phylogenetic analysis and epidemiological typing. The isolates were also screened for the presence of M. hominis variable adherence antigen (vaa) and p120 virulent genes using primer constructs from the respective genes in a conventional PCR protocol. Results: Of the 20 M. hominis vaginal isolates, 4 phylogenetic strains were detected; strain MHS43 constituted 10/20 (50.0%) [2/9 (22.2%) from infertile women and 8/11 (72.7%) from pregnant women]; strain MHBS constituted 3/20 (15%) [3/9 (33.3%) from infertile women and 0/11 (0%) from pregnant women]; strain MHSWP2 constituted 4/20 (20.0%) [3/9 (33.3%) from infertile women and 1/11 (9.1%) from pregnant women]; while strain MHKC87 constituted 3/20 (15%) [1/9 (11.1%) from infertile women and 2/11 (18.2%) from pregnant women].Each of vaa and p120 genes was detected in 14 of 20 isolates, while 6 isolates did not carry the genes. A 2-way ANOVA test showed that none of the genes was significantly associated with a particular strain (p=0.8641). Conclusions: The different views regarding the pathogenicity of M. hominis may be linked to the heterogeneity within the species and lack of homogeneity in the virulent genes as witnessed both in the intra species and intra strain levels.

Evaluation of Inhaler Techniques among Asthma Patients Seen in Nigeria: An Observational Cross Sectional Study

Background: An Adequate and an effective dose of inhalation drugs can be administered only if the correct inhaler-specific technique is followed by asthma patients. There is paucity of data on this subject among Nigerians and Africans. Aims: This observational study was to assess the inhaler techniques among asthma patients in Nigeria and also to identify the factors related to an inaccurate or poor inhaler use. Subjects and Methods: Consenting asthma patients on inhalers; who attended medical out-patients clinic; of two university hospitals in Nigeria were asked to use their inhalers while an inhaler-administration checklist was used to assess each patients inhaler technique. Information on demographics; asthma symptoms history and history of technique education were obtained. Data was analyzed using standard statistical methods. Results: A total of 140 asthma patients participated out of which 75 were females. All the patients used pressurized metered dose inhalers (pMDI) type; 51 of them used dry powder inhalers (DPI) in addition. For pMDI; 22.1 (31/140) completed all required steps while 37.3 (19/51) did so for DPI (P = 0.04). Patients with higher educational qualification (P 0.01) and those with less frequent asthma symptoms (P 0.01) are more likely to use the pMDI inhalers more accurately while patients who have been taught previously by a Doctor were more likely to use the DPI better. Conclusion: Majority of asthma patients use their inhalers inaccurately. Patient-dependent factors were identified as the cause of incorrect technique of inhaler use. Asthma patients on inhalation medications should have routine assessment of their inhaler technique at every visit and corrected if found to be poor

Risk factors for surgical site infections following clean orthopaedic operations.

BACKGROUND: Surgical site infections can follow clean orthopaedic operations and can cause serious morbidity, mortality and increased resource utilization. Despite this, there are few studies on risk factors for surgical site infections in the Nigerian orthopaedic literature. We conducted a prospective study to determine the host and environmental risk factors for surgical site infections following clean orthopaedic operations. MATERIALS AND METHODS: Consecutive patients who satisfied the inclusion criteria and were to undergo clean orthopaedic operations performed at the National Orthopaedic Hospital, Igbobi, Lagos from January 2007 to July 2008 were included. Patient's biodata, duration of preoperative hospitalization and other risk factors were analyzed. The risk factors for surgical site infection were determined with Chi square test. RESULTS: The overall rate of surgical site infection during the 18 months of the study was 9.9% (12 of 121). Independent risk factors for this were: Prolonged duration of preoperative hospital stay greater than 13 days (21% infection rate), increasing age greater than 60 years (31% infection rate), and use of implants and drains (only one un-drained wound was infected). CONCLUSION AND RECOMMENDATIONS: Patient's age, duration of preoperative hospitalization, type of surgery (implant or non-implant), and use of drains were the most significant risk factors affecting surgical site infection. It is recommended that preoperative hospital stay should be as short as possible and extra care/precautions taken when working on the elderly, using implants or requiring drainage.

Risk Factors for Surgical Site Infections Following Clean Orthopaedic Operations

Background: Surgical site infections can follow clean orthopaedic operations and can cause serious morbidity; mortality and increased resource utilization. Despite this; there are few studies on risk factors for surgical site infections in the Nigerian orthopaedic literature. We conducted a prospective study to determine the host and environmental risk factors for surgical site infections following clean orthopaedic operations.Materials and Methods: Consecutive patients who satisfied the inclusion criteria and were to undergo clean orthopaedic operations performed at the National Orthopaedic Hospital; Igbobi; Lagos from January 2007 to July 2008 were included. Patient's biodata; duration of preoperative hospitalization and other risk factors were analyzed. The risk factors for surgical site infection were determined with Chi square test.Results: The overall rate of surgical site infection during the 18 months of the study was 9.9 (12 of 121). Independent risk factors for this were: Prolonged duration of preoperative hospital stay greater than 13 days (21 infection rate); increasing age greater than 60 years (31 infection rate); and use of implants and drains (only one un-drained wound was infected).Conclusion and Recommendations: Patient's age; duration of preoperative hospitalization; type of surgery (implant or non-implant); and use of drains were the most significant risk factors affecting surgical site infection. It is recommended that preoperative hospital stay should be as short as possible and extra care/precautions taken when working on the elderly; using implants or requiring drainage

Retention and loss to follow-up in antiretroviral treatment programmes in southeast Nigeria.

BACKGROUND: This study generated new information about the outcomes of patients enrolled in antiretroviral treatment programmes, as well as the true outcomes of those lost to follow-up (LTF). METHODS: Anonymized data were collected for patients enrolled over a 12-month period from two programmes (public and private) in southeast Nigeria. Estimates of retention, LTF, mortality and transfers were computed. All LTF enrollees (defined as patients who had missed three scheduled visits) whose contact information met pre-defined criteria were traced. RESULTS: A total of 481 (public) and 553 (private) records were included. Median duration of follow-up was about 14 months. Cumulative retention and LTF proportions were 66·5 and 32·8% (public), and 82·6 and 11·0% (private) respectively. LTF rates at third, sixth, ninth and twelfth months were 7·5, 19·3, 25·4 and 29·6% respectively (public), and 4·1, 7·1, 9·0 and 10·0% (private). LTF was higher among males, patients with CD4(+) cell count ≤200 and public programme enrollees. For the public facility, 56·7% of 104 traceable patients were dead and 38·8% were alive; the figures were 34·2 and 60·5% of 46 patients respectively for the private. Most deaths had occurred by the third month. CONCLUSION: Not all patients enrolled for treatment were retained. Though some died, many were LTF, lived within the community, and could develop and transmit resistant viral stains. Most traced patients were dead by the third month and poor contact information limited the effectiveness of tracing. Antiretroviral treatment programmes need to improve documentation processes and develop and implement tracing strategies.

Chronic thromboembolic pulmonary hypertension with pulmonary infarction occuring in a hypertensive.

We present a 72-year-old man and a known hypertensive with poor drug compliance seen here on 22-03-06, with a 4-year history of progressive dyspnoea, associated with cough and a wheeze. On examination he was chronically ill looking with altered state of consciousness, pale, centrally cyanosed, febrile (T-38 degrees C), in respiratory distress (RR-33 pm). Significant chest radiological findings include marked aortic unfolding and cardiomegaly, with biventricular involvement. Numerous nodular opacities in both lung fields especially the Right side with right apical opacification/thickening. Treatment as appropriate was instituted but unfortunately the patient succumbed after thirty days on admission and an autopsy carried out revealed multiple pulmonary infarcts with pulmonary thrombo-embolism.

Chronic thromboembolic pulmonary hypertension with pulmonary infarction occuring in a hypertensive.

We present a 72-year-old man and a known hypertensive with poor drug compliance seen here on 22-03-06,with a 4-year history of progressive dyspnoea, associated with cough and a wheeze. On examination he was chronically ill looking with altered state of consciousness, pale, centrally cyanosed, febrile (T-38 degrees C), in respiratory distress (RR-33pm). Significant chest radiological findings include marked aortic unfolding and cardiomegaly, with biventricular involvement. Numerous nodular opacities in both lung fields especially the Right side with right apical opacification/thickening. Treatment as appropriate was instituted but unfortunately the patient succumbed after thirty days on admission and an autopsy carried out revealed multiple pulmonary infarcts with pulmonary thrombo-embolism.

Effectiveness and safety of adjustable maintenance dosing with budesonide/formoterol turbuhaler compared with traditional fixed doses in bronchial asthma: a multi-centre Nigerian study.

The modern treatment guideline of bronchial asthma recognize that combination of long acting beta2-agonists and inhaled glucocorticoids, enables better control of inflammation and symptoms of asthma than inhaled glucocorticoids only. These guidelines recommended that patients are educated to adjust their medication to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication to asthma symptoms Therefore, combination of formoterol and budesonide can be delivered at different dosing level without the need to change inhalers. This study examined whether asthma control improved if patients adjusted the maintenance doses(AMD) ofbudesonide/formoterol (Symbicort, 80/ 4.5 microg and 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens. This was a prospective open randomized trial carried out in five teaching hospitals across Nigeria between 15th July 2002 and 15th July 2003. Patients with bronchial asthma who met the enrollment criteria were randomized to receive either adjustable dosing or fixed dosing for a period of twelve weeks. The results obtained at the start and the end of the study showed that budesonide/formoterol combination effectively achieved and maintained control of asthma. The adjustable dosing achieves more effective control compared to fixed dosing in terms of the number of patients that are redistributed to less severe forms of persistent asthma. The percentage of patients with intermittent asthma increased from 9.3% at randomization to 55.6% at the end of therapy with more patients at the AMD arm of treatment. Also for mild persistent asthma there was an increase from 20.4% to 24.1%. This showed that at the end of treatment, majority (79.7%) of the patients had intermittent and mild persistent asthma. The frequency of use of budesonide/formoterol in the two arms of treatment showed that patients in the adjustable groups used less number of inhalations of budesonide/formoterol for treatment on average of 2.5 inhalations per day compared to those on fixed dosing who used 4 inhalations per day (p = 0.0001). The number of times patients stayed awake because of asthma was noticed to be more reduced at the adjustable arm of treatment but this was of no statistical significance. It is therefore concluded, that budesonide/formoterol combination in a single inhaler is a simple, well tolerated, convenient treatment which provides effective control of bronchial asthma using a practical self-management plan consistent with current guidelines.

Gender perspectives of sexual and reproductive practices of people living with HIV/AIDS in Enugu, South East Nigeria.

BACKGROUND: a major focus of attention in the efforts at controlling the spread of HIV infection has become the role of gender inequality. The objective of the study was to compare the sexual practices of HIV-positive male and female patients who received counselling and treatment at an Anti-retroviral Clinic in Enugu, South-East Nigeria. METHOD: A comparative cross-sectional descriptive study of patients attending the free anti-retroviral clinic at the University of Nigeria Teaching Hospital Enugu was done. RESULTS: A total of 146 males (30.8%) and 328 females (61.9%) were studied. Although there was no significant difference in the prevalence of sexual activity between the sexes, the reasons for sexual practices differed. Females indulged in risky sexual activity principally in obedience to the demands of their male partners and were more likely to have sexual partners who were unaware of their seropositivity than males. CONCLUSION: Risky sexual behaviour among women living with HIV/AIDS in Enugu despite exposure to intensive counselling was still mainly driven by the subordinate traditional gender roles of women in this culture.

Gender Perspectives of Sexual and Reproductive Practices of People Living With HIV/AIDS in Enugu; South East Nigeria

Nigerian major focus of attention in the efforts at controlling the spread of HIV infection has become the role of gender inequality.1; 2 The objective of the study was to compare the sexual practices of HIV-positive male and female patients who received counselling and treatment at an Anti-retroviral Clinic in Enugu; South-East Nigeria. Method: A comparative cross-sectional descriptive study of patients attending the free anti-retroviral clinic at the University of Nigeria Teaching Hospital Enugu was done. Results: A total of 146 males (30.8) and 328 females (61.9) were studied. Although there was no significant difference in the prevalence of sexual activity between the sexes; the reasons for sexual practices differed. Females indulged in risky sexual activity principally in obedience to the demands of their male partners and were more likely to have sexual partners who were unaware of their seropositivity than males. Conclusion: Risky sexual behaviour among women living with HIV/AIDS in Enugu despite exposure to intensive counselling was still mainly driven by the subordinate traditional gender roles of women in this culture.:

Basal insulin resistance and secretion in Nigerians with type 2 diabetes mellitus.

AIM: The objective of this study was to estimate basal insulin resistance (IR) and insulin secretion (IS) in Nigerians with type 2 diabetes mellitus (T2DM). METHODS: The homeostasis model assessment (HOMA) method was used to estimate basal IR and IS in 146 Nigerians with T2DM and in 33 controls at the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria. Correlations and multiple regression analysis between Box-Cox-transformed IR and log-transformed IS and anthropometric indices were carried out. RESULTS: IR and reduced IS were present, respectively, in 139 (95.5%) and 109 (74.7%) of the diabetic subjects and in 25 (75.8%) and 4 (12.1%) of the controls. In the diabetic subjects, age at diagnosis, duration of diabetes, waist circumference (WC), and body mass index (BMI) correlated significantly with IR (r = -0.2399, P = 0.0035; r = 0.1993, P = 0.0166; r = 0.2267, P = 0.0059; r = 0.2082, P = 0.0120; respectively), whereas duration of diabetes, WC, and BMI correlated significantly with IS (r = -0.2166, P = 0.0091; r = 0.3062, P = 0.0002; r = 0.2746, P = 0.0008; respectively). Age at diagnosis, WC, and duration of diabetes were significant predictors of IR (beta = -0.0161, P < 0.001; beta = 0.0121, P = 0.002; beta = 0.0138, P = 0.042; respectively), whereas duration of diabetes and WC significantly predicted IS (beta = -0.0159, P = 0.025; beta = 0.0155, P < 0.001). CONCLUSIONS: This study shows that both IR and reduced IS are major features of T2DM in Nigerians and that WC consistently correlated and predicted IR. WC measurement is simple and ideal in resource-poor settings for the detection of IR and abdominal obesity. The apparent rarity of coronary heart disease (CHD) in black Africans with T2DM despite a high prevalence of IR warrants further investigation.

Indications for spirometry at a tertiary hospital in south east, Nigeria.

BACKGROUND: Spirometry evaluation of ventilatory functions plays a critical role in the diagnosis, differentiation and management of respiratory illness such as asthma, chronic obstructive pulmonary disease and restrictive lung disorders. It appears to be underutilized especially by most primary care physicians. AIM: This study was aimed at determining the indications for spirometry at a tertiary health institution in Nigeria and to determine the source of referral of the patients. METHODS: Clinical and anthropometric data of all subjects who underwent spirometry at the University of Nigeria Teaching Hospital, Enugu, Nigeria over a three year period were retrieved from the records book and analyzed to determine the sex distribution, age distribution, indication for the procedure, and source of referral. RESULTS: A total of fifty two patients had the procedure over a three year period (Jan 2004-Dec 2006). The male to female ratio was 1: 1.08. Their ages ranged from 5 to 85 years of age with a mean age of 42.3 +/- 20.50 years. The commonest indication for spirometry during the study period was Bronchial asthma followed by Chronic Obstructive Pulmonary disease (COPD). Most of the patients were referred by the respiratory unit performing the procedure followed by the surgical units and no referral came from the neighbouring peripheral hospitals. CONCLUSION: Bronchial Asthma is the commonest indication for the use of spirometry. There is poor referral from the peripheral primary care centers. Primary care general physicians and surgeons should be encouraged to use of spirometry.

Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.

Comparison of the efficacy and safety of budesonide turbuhaler administered once daily with twice the dose of beclomethasone dipropionate using pressurised metered dose inhaler in patients with mild to moderate asthma.

BACKGROUND: Current treatment guidelines have clearly defined the central place and benefits of inhaled glucocorticoids in the management of bronchial asthma. However, compliance with therapy is often poor due to complexity of treatment regimens. Therefore, a single once daily regimen with a simple device, the turbuhaler might be expected to result in improved compliance and better efficiency. STUDY DESIGN: This was a prospective open randomized trial with parallel groups conducted in five tertiary medical institutions. Asthmatic patients who met the enrolment criteria were randomized to receive either budesonide 400 microg daily or beclomethasone dipropionate 400 microg twice daily for eight weeks. RESULT: At the end of the study, both drugs were found to be effective in reducing the symptoms of asthma, reduction of beta2 agonist usage and improvement in lung function tests. However Budesonide Turbuhaler provided better effects in all parameters (p < 0.05). Both drugs were well tolerated. CONCLUSION: It is therefore concluded that Budesonide Turbuhaler administered once daily at a dose of 400 microg is more efficacious than Beclomethasone dipropionate 400 microg twice daily administered via pressurized metered dose inhaler.

Beta cell function and response to treatment in Nigerians with Type 2 diabetes mellitus.

There are scant data from African populations on the association between beta-cell function and response to treatment with oral hypoglycaemic agents in Type 2 diabetes mellitus (T2DM). Fasting plasma C-peptide (FCP) and glucagon-stimulated C-peptide (GSCP) levels were measured in 116 Nigerians with T2DM at a university teaching hospital. After 9 months of follow-up and treatment, they were categorized into three groups based on response to treatment: (A) good control but not on maximum sulphonylurea (SU) therapy, (B) inadequate control but not on maximum SU therapy and (C) on maximum SU therapy+/-insulin or biguanide. Logistic regression models were used to investigate how well C-peptide levels predicted the subjects belonging to Group C who are likely to require insulin. The mean FCP and mean GSCP levels of Group C were significantly lower than in the other groups (p=0.024; p= <0.001 respectively). A GSCP cut-off value of < or =1.3 ng/mL predicted membership of Group C with 85% sensitivity and 89% specificity while a cut-off of < or =1.8 ng/mL was associated with 91% sensitivity and 66% specificity. In resource-poor settings where inadequate treatment are common, estimation of GSCP may be useful in predicting treatment response and should be weighed against the cost of inadequate therapy with higher morbidity and mortality.

Chronic treatment with carvedilol improves ventricular function and reduces myocyte apoptosis in an animal model of heart failure.

BACKGROUND: Beta blocker treatment has emerged as an effective treatment modality for heart failure. Interestingly, beta-blockers can activate both pro-apoptotic and anti-apoptotic pathways. Nevertheless, the mechanism for improved cardiac function seen with beta-blocker treatment remains largely unknown. Carvedilol is a non-selective beta-blocker with alpha-receptor blockade and antioxidant properties. We therefore studied the impact of the effects of carvedilol in an animal model of end-stage heart failure. RESULTS: To test whether chronic treatment with beta-blockade decreases apoptosis, we treated myopathic turkeys with two dosages of carvedilol, 1 mg/kg (DCM1) and 20 mg/kg (DCM20), for four weeks and compared them to non-treated DCM animals (DCM0) and to control turkeys (CON). Echocardiographic measurements showed that non-treated DCM animals had a significantly lower fractional shortening (FS) when compared to CON (68.73 +/- 1.37 vs. 18.76 +/- 0.59%, p < 0.001). Both doses of carvedilol significantly improved FS (33.83 +/- 10.11 and 27.73 +/- 6.18% vs. 18.76 +/- 0.59% for untreated DCM, p < 0.001). DCM left ventricles were characterized by a higher percentage of apoptotic nuclei when compared to CON (5.64 +/- 0.49 vs. 1.72 +/- 0.12%, respectively p < 0.001). Both doses of carvedilol significantly reduced the number of apoptotic nuclei (2.32 +/- 0.23% and 2.36 +/-6% 1 mg and 20 mg/kg respectively). CONCLUSIONS: Carvedilol improves ventricular function. Furthermore, treatment with carvedilol decreased the incidence of apoptosis in cardiac myocytes from failing hearts at both doses. These data suggest that the inhibition of apoptosis with carvedilol may lead to improvement in ventricular function and may underlie a beneficial effect of beta-blockade independent of heart rate lowering effects.

Myofibrillar responsiveness to cAMP, PKA, and caffeine in an animal model of heart failure.

We investigated whether an alteration of myofilament calcium responsiveness and contractile activation may in part contribute to heart failure. A control group of Broad Breasted White turkey poults was given regular feed without additive, whereas the experimental group was given the control ration with 700 ppm of furazolidone at 1 week of age for 3 weeks (DCM). At 4 weeks of age, left ventricular trabeculae carneae were isolated from hearts and calcium-force relationships studied. No differences in calcium-activation between fibers from control or failing hearts were noted under standard experimental conditions. Also failing hearts demonstrated no significant shift in the population of troponin T isoforms but we did observe a significant 4-fold decrease in TnT content in failing hearts compared to non-failing hearts. Addition of caffeine, however, resulted in a greater leftward shift on the calcium axis in fibers from failing hearts. At pCa 6, caffeine increased force by 26+/-2.1% in control fibers and 44.5+/-8.7% in myopathic fibers. Cyclic AMP resulted in a greater rightward shift on the calcium axis in failing myocardium. In control muscles, the frequency of minimum stiffness (f(min)) was higher than in muscles from failing hearts. cAMP and caffeine both shifted f(min) to higher frequencies in control fibers whereas in fibers from failing hearts both caused a greater shift. These results lead us to conclude that heart failure exerts differential effects on cAMP and caffeine responsiveness. Our data suggest that changes at the level of the thin myofilaments may alter myofilament calcium responsiveness and contribute to the contractile dysfunction seen in heart failure.