Cardiopulmonary fitness is strongly associated with body cell mass and fat-free mass: The Study of Health in Pomerania (SHIP).

Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by bioelectrical impedance analysis. The suitability of the different markers as a normalization variable was evaluated by taking into account correlation coefficients (r) and intercept (α-coefficient) values from linear regression models. A combination of high r and low α values was considered as preferable for normalization purposes. BCM was the best normalization variable for VO2peak (r = .72; P ≤ .001; α-coefficient = 63.3 mL/min; 95% confidence interval [CI]: 3.48-123) followed by FFM (r = .63; P ≤ .001; α-coefficient = 19.6 mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a markedly higher intercept were found for TBW (r = .42; P ≤ .001; α-coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified as a poor normalization variable (r = .10; P ≤ .001; α-coefficient = 2133; 95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the different normalization variables. Our results suggest that BCM, followed by FFM, might be the most appropriate marker for the normalization of VO2peak when comparing CPF between subjects with different body shape.

Prediabetes is associated with lower brain gray matter volume in the general population. The Study of Health in Pomerania (SHIP).

BACKGROUND AND AIMS: We investigated the associations of fasting (FG) and 2-h postload (2HG) plasma glucose from oral glucose tolerance test (OGTT) with gray (GMV) and white (WMV) matter volume. METHODS AND RESULTS: We analyzed data from 1330 subjects without known diabetes mellitus, aged 21 to 81, from the second cohort (SHIP-Trend-0) of the population-based Study of Health in Pomerania (SHIP). Following the OGTT, individuals were classified in five groups (according to the American Diabetes Association criteria): normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) and unknown type 2 diabetes mellitus (UDM). GMV and WMV were determined by magnetic resonance imaging. FG, 2HG and OGTT groups were associated with GMV and WMV by linear regression models adjusted for confounders. FG and 2HG were inversely associated with GMV. The adjusted mean GMV, when compared with the NGT group (584 ml [95% CI: 581 to 587]), was significantly lower in the groups i-IFG (578 ml [95% CI: 573 to 582]; p = 0.035) and UDM (562 ml [95% CI: 551 to 573]; p < 0.001), but not different in the i-IGT (586 ml [95% CI: 576 to 596]; p = 0.688) and IFG + IGT (579 ml [95% CI: 571 to 586]; p = 0.209) groups. There were no associations of FG, 2HG and OGTT parameters with WMV. CONCLUSION: Our findings suggest that elevated FG levels, even within the prediabetic range, might already have some harmful effects on GMV.

[Weaning Unit of the University Medicine Greifswald - Institutional Structure and Weaning Results from Prolonged Ventilation over 10 Years]. / Weaningzentrum Greifswald ­ Struktur und Ergebnisse bei der Entwöhnung von der Langzeitbeatmung über zehn Jahre.

The increasing importance of intensive care medicine including mechanical ventilation has been accompanied by the demand of weaning opportunities for patients undergoing prolonged mechanical ventilation. Consequently, specialised clinical institutions, focusing on the weaning from mechanical ventilation, have been established since the 1980 s.The present article illustrates the structural development and results of such a specialised institution at the University Medicine Greifswald, using data of 616 patients collected within the past ten years (2006 - 2015). Across the years, a shift in the underlying disease leading to mechanical ventilation can be found, with rising numbers of patients suffering from pneumonia/sepsis and declining numbers of patients who underwent cardiac surgery in advance. The days with mechanical ventilation outside (p = 0.004) and within the investigated institution (p = 0.02) are significantly declining. The percentage of successfully weaned patients increased from 62.7 % (2006 - 2010) to 77.3 % (2011 - 2015), p < 0.001. Consecutively, the percentage of patients who remained mechanically ventilated decreased from 16.4 % to 9.6 % (p < 0.001) and the share of in-hospital deceased patients significantly declined from 20.9 % to 13.0 % (p < 0.001). Furthermore, the one-year-survival after hospital discharge in successful weaned patients was 72 percent. The present data, collected at the University Medicine Greifswald are quite comparable to data of other German institutions that are specialised on weaning from mechanical ventilation.

[Lung Health Data of the Study of Health in Pomerania - a Review of Samples, Methods and First Results]. / Pneumologisch relevante Daten aus der "Study of Health in Pomerania" (SHIP) ­ eine Übersicht zu den Kohorten, Methoden und ersten Ergebnissen.

Investigating reasons for differing life expectancy and prevalence of cardiovascular risk factors between old and new states of the Federal Republic of Germany an epidemiological study in Western Pomerania - the population-based project Study of Health in Pomerania (SHIP) - was planned.Prevalence and incidence of common risk factors, subclinical disorders and clinical diseases have been assessed since 1997 in five-year intervals. The third follow up (SHIP-3) was assessed between 2014 and 2016. In addition, an independent representative population sample was investigated between 2008 - 2012 (SHIP-TREND). Recently, the first follow up of this cohort has been started (SHIP-TREND-1). This paper reports the methodological approaches for detecting pneumological relevant morbidities in this population-based study. It aims to offer insights for potential cooperation with interested research groups.

[Recurrent thromboembolisms despite full anticoagulation in a patient with antiphospholipid syndrome]. / Rezidivierende Thrombembolien trotz Vollantikoagulation bei Patientin mit Antiphospholipidsyndrom.

We report on a female patient with confirmed secondary antiphospholipid syndrome (APS) due to underlying systemic lupus erythematosus (SLE). Despite a thromboplastin time within the normal range (international normalized ratio, INR) under treatment with a vitamin K antagonist (VKA), a recurrent thrombotic event occurred, this time as pulmonary embolism due to bilateral deep vein thrombosis. Despite an INR value in the therapeutic range, clotting factors II, VII, IX and X were found to be insufficiently decreased suggesting inefficient anticoagulation. Thus, the anticoagulation regimen was changed to the direct oral anticoagulant dabigatran. This case demonstrates that the INR in APS patients may be artificially prolonged in rare cases, despite a normal activated partial thromboplastin time (aPTT) and cannot be used for monitoring VKA anticoagulant therapy. Suspicion of ineffective anticoagulation despite VKA therapy should prompt measurement of the individual clotting factors.

Vitamin D is associated with cardiopulmonary exercise capacity: results of two independent cohorts of healthy adults.

Vitamin D has an important role in calcium homeostasis and is known to have various health-promoting effects. Moreover, potential interactions between vitamin D and physical activity have been suggested. This study aims to investigate the relationship between 25-hydroxyvitamin D (25(OH)D) and exercise capacity quantified by cardiopulmonary exercise testing (CPET). For this, 1377 participants from the Study of Health in Pomerania (SHIP-1) and 750 participants from the independent SHIP-TREND cohort were investigated. Standardised incremental exercise tests on a cycle ergometer were performed to assess exercise capacity by VO2 at anaerobic threshold, peakVO2, O2 pulse and peak power output. Serum 25(OH)D levels were measured by an automated chemiluminescence immunoassay. In SHIP-1, 25(OH)D levels were positively associated with all considered parameters of cardiopulmonary exercise capacity. Subjects with high 25(OH)D levels (4th quartile) showed an up to 25% higher exercise capacity compared with subjects with low 25(OH)D levels (1st quartile). All associations were replicated in the independent SHIP-TREND cohort and were independent of age, sex, season and other interfering factors. In conclusion, significant positive associations between 25(OH)D and parameters of CPET were detected in two large cohorts of healthy adults.

[From myxomas of the skin to LVAD implantation : A 28-year-old female patient with Carney complex]. / Von Hautmyxomen zur LVAD-Implantation : Eine 28-jährige Patientin mit Carney-Komplex.

Multiple skin lesions, endocrine dysfunction and cardiac myxomas are characteristic symptoms of Carney complex. This case report gives an overview about the major and minor criteria of Carney complex and presents the course of a female patient who developed severe cardiac insufficiency with multiple organ failure because of recurring heart operations leading to implantation of a left ventricular assist device (LVAD).

ECG-gated coronary angiography enables submillisievert imaging in invasive cardiology.

BACKGROUND: The median dose area products (DAP) and effective doses (ED) of patients arising from coronary angiography (CA) are considerable: According the 2013 National German Registry, they amount to 19.8 Gy × cm(2) and 4.0 mSv, respectively. METHODS: We investigated the feasibility of prospective electrocardiogram (ECG)-gated coronary angiography (CA)-a novel technique in invasive cardiology-with respect to possible reduction in irradiation effects. Instead of universally fix-rated radiographic acquisition within 7.5-15 frames/s, one single frame/heartbeat was triggered toward the diastolic moment immediately before atrial contraction (77 % of ECG-RR interval) most likely to provide motion-free and hence optimized resolution of the coronary tree. For 200 patients (body mass index 27.8 kg/m(2), age 67.5 years, male 55 %, 68 bpm) undergoing ECG-gated CA, we measured various median (interquartile range) parameters for radiation exposure. RESULTS: The total DAP was 0.64 (0.46-1.00), radiographic fraction was 0.30 (0.19-0.43), and fluoroscopic fraction was 0.35 (0.21-0.57) Gy × cm(2). Radiographic imaging occurred within 21.7 s (17.1-26.3), with 25 frames (20-30) over the course of 7 runs (6-8). Fluoroscopy time was 119 s (94-141). Radiographic DAP was 12.6 mGy × cm(2)/frame and 13.8 mGy × cm(2)/s. Fluoroscopic DAP was 0.8 mGy × cm(2)/pulse and 3.1 mGy × cm(2)/s. Patient reference point air kerma was 17.0 mGy (11.1-28.1) and contrast volume was 70 ml (60-85). CONCLUSION: In conclusion, invasive ECG-gated coronary imaging is feasible in clinical routine and enables patient EDs of approx. 3 % of typical values in invasive cardiology: 0.13 mSv (0.09-0.20).

Latest-generation catheterization systems enable invasive submillisievert coronary angiography.

BACKGROUND: The radiation risk of patients undergoing invasive cardiology remains considerable and includes skin injuries and cancer. To date, submillisievert coronary angiography has not been considered feasible. PATIENTS AND METHODS: In 2011, we compared results from 100 consecutive patients undergoing elective coronary angiography using the latest-generation flat-panel angiography system (FPS) with results from examinations by the same operator using 106 historic controls with a conventional image-intensifier system (IIS) that was new in 2002. RESULTS: The median patient exposure parameters were measured as follows: dose-area product (DAP) associated with radiographic cine acquisitions (DAP(R)) and fluoroscopy (DAP(F)) scenes, radiographic frames and runs, and cumulative exposure times for radiography and fluoroscopy. On the FPS as compared to the traditional IIS, radiographic detector entrance dose levels were reduced from 164 to 80 nGy/frame and pulse rates were lowered from 12.5/s to 7.5/s during radiography and from 25/s to 4/s during fluoroscopy. The cardiologist's performance patterns remained comparable over the years: fluoroscopy time was constant and radiography time even slightly increased. Overall patient DAP decreased from 7.0 to 2.4 Gy × cm(2); DAP(R), from 4.2 to 1.7 Gy × cm(2); and DAP(F), from 2.8 to 0.6 Gy × cm(2). Time-adjusted DAP(R)/s decreased from 436 to 130 mGy × cm(2) and DAP(F)/s, from 21.6 to 4.4 mGy × cm(2). Cumulative patient skin dose with the FPS amounted to 67 mGy, and the median (interquartile range) of effective dose was 0.5 (0.3 … 0.7) mSv. CONCLUSION: Consistent application of radiation-reducing techniques with the latest-generation flat-panel systems enables submillisievert coronary angiography in invasive cardiology.

[Reference values for arterial oxygen content]. / Referenzwerte für den arteriellen Sauerstoffgehalt.

BACKGROUND: In clinical practice, oxygen saturation as measured by photoplethysmography and arterial oxygen tension as determined by blood gas analysis are the parameters used frequently to estimate the oxygen status of a patient. Additionally, the cardiac output CO and the arterial oxygen content CaO2 are critical for the delivery of oxygen DO2 to organs and tissues. So far, CaO2 reference values published by Mertzlufft and Zander (1984) and Siggaard-Andersen (1990) are widely used. The aim of the present study was to reevaluate previously published results using the results of a population-based study. Furthermore, the impact of smoking on CaO2 will be assessed. PATIENTS AND METHODS: Data of 1018 volunteers from the Study of Health in Pomerania (SHIP) were analyzed. CaO2 was calculated from blood gas analysis of capillary blood obtained from a hyperemised ear lobe. Reference value equations controlled for sex, age and smoking were derived with quantile regression analysis and fractional polynomials. RESULTS: Lower limits of normal (LLN) decline with age. Current smoking has no significant influence on LLN for CaO2. CONCLUSION: Sex, age and smoking-specific normal values can be calculated using the current equations.

[Diagnosis of systolic and diastolic heart failure]. / Diagnostik der systolischen und diastolischen Herzinsuffizienz.

In this review, heart failure is confined to etiologies not due to rhythm disturbances or valvular heart disease. Besides measurement of natriuretic peptides, echocardiography is established as an important diagnostic procedure. Echocardiography is especially helpful in discriminating between heart failure with preserved ejection fraction (HF-PEF) and reduced ejection fraction (HF-REF). Because of its ease to be performed, the 6 min walk test continues to be a standard diagnostic procedure. Cardiopulmonary exercise testing provides more detailed information regarding differential diagnostic and prognostic considerations.

[The Study of Health in Pomerania (SHIP) reference values for cardiopulmonary exercise testing]. / Referenzwerte für die Spiroergometrie - Ergebnisse der Study of Health in Pomerania (SHIP).

The interpretation of gas exchange measured by cardiopulmonary exercise testing (CPET) depends on reliable reference values. Within the population based Study of Health in Pomerania (SHIP) CPET was assessed in 1706 volunteers. The assessment based on symptom limited exercise tests on a bicycle in a sitting position according to a modified Jones protocol. CPET was embedded in an extensive examination program. After the exclusion of active smokers and volunteers with evidence of cardiopulmonary and musculoskeletal disorders the reference population comprised 616 healthy subjects (333 women) aged 25 to 85 years. Reference equations including upper and/or lower limits based on quantile regression were assessed. All values were corrected for the most important influencing factors.This study provides reference equations for gas exchange and exercise capacity assessed within a population in Germany.

Airflow limitation, lung volumes and systemic inflammation in a general population.

Although several levels of evidence have suggested an association between systemic inflammation and spirometric lung volumes, data addressing the potential interrelationship between airflow limitation and inflammatory markers are sparse and remain controversial. Potential associations between high-sensitivity C-reactive protein (hsCRP), fibrinogen and lung function were investigated in 1,466 individuals aged 25-85 yrs, representing a general population. Within this cross-sectional population, data on body plethysmography, spirometry, helium dilution and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were analysed. After adjustment for potential confounding factors, such as smoking, obesity and cardiorespiratory fitness, there was an inverse association of hsCRP with forced expiratory and static lung volumes. In neither apparently healthy nor the entire population was inflammation associated with airflow limitation in central airways. In smokers only, higher hsCRP and fibrinogen were associated with an impaired D(L,CO). This study shows that higher levels of hsCRP are associated with decreased lung volumes in a general population over a wide age range. A consistent interrelationship of central airflow limitation and inflammation was not verifiable. Smoking is related to an impaired D(L,CO) in association with an increase in systemic inflammation.

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Association of airflow limitation with trauma exposure and post-traumatic stress disorder.

Trauma exposure and post-traumatic stress disorder (PTSD) are associated with self-reported asthma and chronic obstructive pulmonary disease. However, these conditions have not yet been related to objective measures of lung function. 1,772 adults from the general population were assessed regarding their medical histories and spirometric lung function. Additionally, they were administered a PTSD interview, and assigned to three groups: no trauma; trauma, but no PTSD; and trauma with PTSD. Adjusting for sociodemographic, clinical and lifestyle factors, subjects with PTSD had significantly higher odds ratios for most asthma-related symptoms than PTSD-negative participants (OR 3.2-8.8). The mean ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) was lowest in the PTSD group and highest in those without trauma exposure. Traumatic stress was independently associated with FEV1 and FEV1/FVC. Participants with PTSD, compared with those without, had a significantly increased risk for airflow limitation independent of its definition (OR 4.2-7.8). This is the first study relating traumatic stress and PTSD, respectively, to objective parameters of lung function. Our findings suggest an association of trauma exposure and PTSD with airflow limitation, which may be mediated by inflammatory processes.

Anti-inflammatory properties of montelukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis.

BACKGROUND: Leukotrienes, especially LTC4, are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways. Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase. OBJECTIVE: To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps, and determine its dependency on aspirin sensitization. METHODS: Twenty-four patients (7 women, 17 men; median age, 55.5 years) with nasal polyps and controlled asthma (n=12 with aspirin intolerance) were treated with 10 mg montelukast once daily for 6 weeks in a blinded, placebo-controlled fashion. The placebo phase was randomly assigned 4 weeks before (n=12) or after treatment (n=12). Symptom score, rhinoendoscopy, rhinomanometry, smears for eosinophils, and nasal lavages for the determination of different mediators were performed. RESULTS: Compared to placebo, there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment. Furthermore, reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment. CONCLUSION: Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma, with or without aspirin intolerance.

Effect of fluticasone on neuropeptides in nasal lavage in persistent allergic rhinitis.

OBJECTIVE: Recent guidelines reveal that allergic rhinitis impairs quality of life. Neuropeptides play a central role in allergy-related nasal inflammation. The objective of this study was to analyze the release of neuropeptides (substance P, neurokinin A, and vasoactive intestinal peptide) in nasal lavage and their modification by intranasal fluticasone propionate as an established therapy in patients with allergic rhinitis. METHODS: Eleven patients with proven allergic rhinitis induced by house dust mite were challenged before and after administration of fluticasone propionate nasal spray. Nasal lavage samples were collected after allergen challenge, and neuropeptides were measured using enzyme-linked immunosorbent assay. Values for histamine, protein, and human serum albumin were also recorded. Eight healthy individuals were included as nonatopic controls. RESULTS: The neuropeptides investigated were detectable in nasal lavage fluid in both patients and controls. Treatment with fluticasone propionate significantly decreased clinical response to allergen challenge (P < .01) compared with the controls and led to a decrease in values for substance P, neurokinin A, vasoactive intestinal peptide, histamine release, human serum albumin, and total protein after allergen challenge (P < .01). CONCLUSIONS: The demonstration of proinflammatory neuropeptides in NAL and suppression of their release after allergen challenge caused by a topical corticosteroid suggest a role for neuropeptides in allergic inflammation. Diminished release of neuropeptides induced b fluticasone propionate was accompanied by an improvement in the clinical symptoms of patients with persistent allergic rhinitis.

Transradial access in percutaneous coronary interventions: technique and procedure.

After showing significantly lower complication rates in diagnostic coronary angiography, the radial artery access was successfully introduced as a useful vascular access site for transradial percutaneous coronary intervention in order to enhance patients' comfort and reduce hospital workload and costs. Moreover, due to the reduced need for antiplatelet therapy cessation as a result of lower bleeding complications, patients treated with transradial access showed a significantly better cardiac outcome in randomized interventional acute coronary syndrome studies.Procedural success and postprocedural radial arteritis or radial occlusions are closely related to anatomical circumstances (e.g., anomalous radial branching patterns, tortuosity, e.g., radial loops and small radial artery diameters), or risk factors for radial spasms (e.g. smoking, anxiety, vessel diameter, age, gender) which can effectively be reduced by the use of smaller catheters (4-5 Fr) and the administration of an adjuvant pharmacological therapy before (3000 U heparin, verapamil, nitroglycerine) and after (ibuprofen) the intervention.For successful radial sheath access and transradial catheterization, it is important to use dedicated radial access needles ≤ 21-gauge and steel wires ≤ 0.018 in. In order to pass the brachiocephalic trunk without difficulties or complications and access the ascending aorta, the use of inspiration maneuvers is of central importance.

The German Transregional Collaborative Research Centre 'Inflammatory Cardiomyopathy--Molecular Pathogenesis and Therapy'. Methods and baseline results from a 3-centre clinical study.

OBJECTIVES: This report focuses on the design and methods of the 3-centre clinical study of the Transregional Collaborative Research Centre 'Inflammatory Cardiomyopathy--Molecular Pathogenesis and Therapy', which aims to establish a comprehensive research registry on the diagnostics, therapy and disease outcomes of patients with inflammatory cardiomyopathy (CMi). The study goals are to investigate specific disease sub-entities and to develop standardised strategies for diagnostics and treatment. METHODS: All consecutive patients with clinically suspected CMi, post-myocarditic cardiomyopathy and acute myocarditis are included in the research registry. Cardiopulmonary functional tests, clinical and patient data are obtained at baseline and subsequent readmission appointments and are linked to allow for prospective follow-up. Co-morbidities, quality of life, health- related behaviour and sociodemographic variables are ascertained using uniform self-administered questionnaires. PRESENT STATUS: By May 2008, 2,061 cases had been included in the research registry (1,300 data-sets completed). At registration, 335 patients were diagnosed with CMi. The mean age was 50 +/- 13 years and the mean ejection fraction was 39.9 +/- 15.8%. CONCLUSIONS: The broad range of the acquired molecular-biological, histological, immunohistological, clinical and patient data makes this the most comprehensive research registry on patients with CMi to date.

Vardenafil protects isolated rat hearts at reperfusion dependent on GC and PKG.

BACKGROUND AND PURPOSE: The type-5 PDE inhibitor vardenafil reduces myocardial infarct size in situ, following ischemia/reperfusion, when applied at reperfusion in animal models. Little is known about the underlying protective signaling. Here, we test whether vardenafil is protective in rat isolated hearts and in a cell model of calcium stress. EXPERIMENTAL APPROACH: Infarct size in rat isolated hearts was measured after a 30 min regional ischemia and 120 min reperfusion. Vardenafil (1 nM-1 microM) was infused during reperfusion. HL-1 cardiomyocytes were loaded with tetramethylrhodamine ethyl ester (TMRE), a fluorescent marker of mitochondrial membrane potential (psi m). KEY RESULTS: Vardenafil at reperfusion reduced infarct size as percentage of the ischemic zone from 45.8+/-2.0% in control hearts to 26.2+/-2.7% (P<0.001) only at 10 nM, whereas higher or lower dosages failed to protect. This protective effect was blocked by co-administration of either the GC inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or the PKG inhibitor, KT-5823. HL-1 cardiomyocytes, loaded with TMRE, were treated for 80 min with the calcium ionophore, calcimycin, to induce calcium stress. This reduced the mean cell fluorescence to 63.3 +/- 3.8% of baseline values and vardenafil protected against this fall (78.6 +/- 3.6%, P<0.01). The vardenafil-induced protection of HL-1 cells was blocked by ODQ, KT-5823 or the PKG-inhibiting peptides DT-2 and DT-3, confirming a role for GC and PKG. CONCLUSIONS AND IMPLICATIONS: These results further support the hypothesis that PDE-5 inhibitors are protective in ischemic hearts, in addition to their known clinical effects in the treatment of erectile dysfunction in men.