A systematic review for the evidence of recommendations and guidelines in hybrid nuclear cardiovascular imaging.

OBJECTIVES: This study aimed to evaluate the level of evidence of expert recommendations and guidelines for clinical indications and procedurals in hybrid nuclear cardiovascular imaging. METHODS: From inception to August 2023, a PubMed literature analysis of the latest version of guidelines for clinical hybrid cardiovascular imaging techniques including SPECT(/CT), PET(/CT), and PET(/MRI) was performed in two categories: (1) for clinical indications for all-in primary diagnosis; subgroup in prognosis and therapy evaluation; and for (2) imaging procedurals. We surveyed to what degree these followed a standard methodology to collect the data and provide levels of evidence, and for which topic systematic review evidence was executed. RESULTS: A total of 76 guidelines, published between 2013 and 2023, were included. The evidence of guidelines was based on systematic reviews in 7.9% of cases, non-systematic reviews in 47.4% of cases, a mix of systematic and non-systematic reviews in 19.7%, and 25% of guidelines did not report any evidence. Search strategy was reported in 36.8% of cases. Strengths of recommendation were clearly reported in 25% of guidelines. The notion of external review was explicitly reported in 23.7% of cases. Finally, the support of a methodologist was reported in 11.8% of the included guidelines. CONCLUSION: The use of evidence procedures for developing for evidence-based cardiovascular hybrid imaging recommendations and guidelines is currently suboptimal, highlighting the need for more standardized methodological procedures.

Use of cardiac imaging in chronic coronary syndromes: the EURECA Imaging registry.

BACKGROUND: The prospective, multicentre EURECA registry assessed the use of imaging and adoption of the European Society of Cardiology (ESC) Guidelines (GL) in patients with chronic coronary syndromes (CCS). METHODS: Between May 2019 and March 2020, 5156 patients were recruited in 73 centres from 24 ESC member countries. The adoption of GL recommendations was evaluated according to clinical presentation and pre-test probability (PTP) of obstructive coronary artery disease (CAD). RESULTS: The mean age of the population was 64 ± 11 years, 60% of patients were males, 42% had PTP >15%, 27% had previous CAD, and ejection fraction was <50% in 5%. Exercise ECG was performed in 32% of patients, stress imaging as the first choice in 40%, and computed tomography coronary angiography (CTCA) in 22%. Invasive coronary angiography (ICA) was the first or downstream test in 17% and 11%, respectively. Obstructive CAD was documented in 24% of patients, inducible ischaemia in 19%, and 13% of patients underwent revascularization. In 44% of patients, the overall diagnostic process did not adopt the GL. In these patients, referral to stress imaging (21% vs. 58%; P < 0.001) or CTCA (17% vs. 30%; P < 0.001) was less frequent, while exercise ECG (43% vs. 22%; P < 0.001) and ICA (48% vs. 15%; P < 0.001) were more frequently performed. The adoption of GL was associated with fewer ICA, higher proportion of diagnosis of obstructive CAD (60% vs. 39%, P < 0.001) and revascularization (54% vs. 37%, P < 0.001), higher quality of life, fewer additional testing, and longer times to late revascularization. CONCLUSIONS: In patients with CCS, current clinical practice does not adopt GL recommendations on the use of diagnostic tests in a significant proportion of patients. When the diagnostic approach adopts GL recommendations, invasive procedures are less frequently used and the diagnostic yield and therapeutic utility are superior.

Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19: the COVAIR study.

AIM: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. METHODS: Between November 2020 and May 2021, in this pilot, case-control study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59 ± 12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. RESULTS: There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, P = 0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, P = 0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho = - 0.528, P = 0.017 and Spearman's rho = - 0.480, p = 0.032, respectively). Patients who were scanned less than or equal to 60 days from admission (n = 11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, P = 0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, P = 0.038). There was a significant difference in IAS- TBR between patients scanned ≤ 60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], P = 0.036). CONCLUSION: This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

Multi-center study of inter-rater reproducibility, image quality, and diagnostic accuracy of CZT versus conventional SPECT myocardial perfusion imaging.

BACKGROUND: Cadmium-zinc-telluride (CZT)-based detectors exhibit higher diagnostic sensitivity in myocardial perfusion imaging (MPI) than conventional Anger-MPI for detection of coronary artery disease (CAD); however, reduced specificity and diagnostic accuracy of CZT-MPI were observed. This study aims to compare these different camera systems and to examine the degree of inter-rater reproducibility among readers with varying experience in MPI. METHODS: 83 patients who underwent double stress/rest examinations using both a CZT and conventional SPECT cameras within one visit were included. Anonymized and randomized MPI-images were distributed to 15 international readers using a standardized questionnaire. Subsequent coronary angiography findings of ten patients served as a reference for analysis of sensitivity and specificity. RESULTS: Image quality was significantly better in CZT-MPI with significantly lower breast attenuation (P < 0.05). CZT-MPI exhibited higher sensitivity than Anger-MPI (87.5% vs. 62.5%) and significantly reduced specificity (40% vs. 100%). Readers experienced with both camera systems had the highest inter-rater agreement indicating higher reproducibility (CZT 0.54 vs. conv. 0.49, P < 0.05). CONCLUSIONS: Higher diagnostic sensitivity of CZT-MPI offers advantages in detection of CAD yet potentially of at the cost of reduced specificity, therefore it requires special training and a differentiated evaluation approach, especially for non-experienced readers with such camera systems.

Neutrophil extracellular traps in giant cell arteritis biopsies: presentation, localization and co-expression with inflammatory cytokines.

OBJECTIVES: To explore the presence of neutrophil extracellular traps (NETs) in inflamed temporal artery biopsies (TABs) of patients with GCA. METHODS: Ten patients with GCA [five with limited and five with associated generalized vascular involvement, as defined by 18F-fluorodeoxyglucose PET with CT (PET/CT)] and eight with PMR were studied. The presence, location, quantitation and decoration of NETs with IL-6, IL-1ß and IL-17A were assessed in TABs at the time of disease diagnosis by tissue immunofluorescence and confocal microscopy. Paired serum levels of IL-6 and IL-17A were also evaluated in all patients. RESULTS: All temporal artery biopsies from GCA, but not PMR, patients had NETs located mainly in the adventitia, adjacent to the vasa vasorum. NETs decorated with IL-6 were present in 8/10 TABs of GCA patients, of whom 5 were PET/CT(+) and 3 PET/CT(-) patients. IL-17A(+) NETs were observed in all GCA patients. IL-1ß(+) NETs were not detected in any GCA patient. No relation was found between serum IL-6 and IL-17A levels and NETs containing IL-6 and/or IL-17A. CONCLUSIONS: NETs bearing pro-inflammatory cytokines are present in inflamed GCA-TABs. Future studies with a larger number of patients from different centres will show whether the findings regarding neutrophils/NETs in the TAB are consistent and disclose their clinical impact.

Visceral adipose tissue phenotype and hypoadiponectinemia are associated with aortic Fluorine-18 fluorodeoxyglucose uptake in patients with familial dyslipidemias.

BACKGROUND: The role of adipose tissue (AT) in arterial inflammation in familial dyslipidaemias is poorly studied. We investigated the relationship between AT and arterial inflammation in patients with heterozygous familial hypercholesterolemia (heFH) and familial combined hyperlipidemia (FCH). METHODS AND RESULTS: A total of 40 patients (20 heFH/20 FCH) and a subgroup of 20 of non-heFH/FCH patients were enrolled. Participants underwent blood sampling for serum adipokine measurements and Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT imaging. Abdominal visceral (VAT) and subcutaneous (SAT) AT volumes and AT and abdominal aorta 18F-FDG uptake were quantified. FCH patients had increased VAT (pANOVA = 0.004) and SAT volumes (pANOVA = 0.003), lower VAT metabolic activity (pANOVA = 0.0047), and lower adiponectin levels (pANOVA = 0.007) compared to heFH or the control group. Log(Serum adiponectin) levels were correlated with aortic TBR (b = - 0.118, P = 0.038). In mediation analysis, VAT volume was the major determinant of circulating adiponectin, an effect partly mediated via VAT TBR. Clustering of the population of heFH/FCH by VAT volume/TBR and serum adiponectin identified two distinct patient clusters with significant differences in aortic TBR levels (2.11 ± 0.06 vs 1.89 ± 0.05, P= 0.012). CONCLUSIONS: VAT phenotype (increased VAT volume and/or high VAT TBR) and hypoadiponectinemia may account for the observed differences in arterial inflammation levels between heFH and FCH patients.

A Novel, Cell-Free Therapy to Enter Our Hearts: The Potential Role of Small EVs in Prevention and Treatment of CVD.

Heart disease constitutes one of the leading causes of morbidity and mortality worldwide. Current therapeutic techniques, such as interventional revascularization, although lifesaving, come along with myocardial injury related to the reperfusion itself, called ischemia-reperfusion injury, which is an added factor for increased morbidity. For that reason, there is an imperative need for novel therapies to be developed that would either prevent or treat myocardial injury. Extracellular vesicles (EVs), specifically small EVs (sEVs), have proven to be important mediators of intercellular communication. The fact that they carry information reflecting that of the parental cell makes them an ideal candidate for diagnostic purposes. sEVs derived from immunoregulatory cells, such as mesenchymal stem cells or cardiac progenitor cells, could also be used therapeutically to exert the primary immunomodulatory function but without carrying the side effects related to cell therapy. Furthermore, as a natural product, they have the added advantage of low immunogenicity, offering the potential for safe drug delivery. In the field of cardiology, there has been great interest in the therapeutic and diagnostic potential of sEVs with significant translational potential. Here, we review the potential use of sEVs in the context of myocardial ischemia and ischemia-reperfusion injury.

Relationship of Endothelial Shear Stress with Plaque Features with Coronary CT Angiography and Vasodilating Capability with PET.

Background Advances in three-dimensional reconstruction techniques and computational fluid dynamics of coronary CT angiography (CCTA) data sets make feasible evaluation of endothelial shear stress (ESS) in the vessel wall. Purpose To investigate the relationship between CCTA-derived computational fluid dynamics metrics, anatomic and morphologic characteristics of coronary lesions, and their comparative performance in predicting impaired coronary vasodilating capability assessed by using PET myocardial perfusion imaging (MPI). Materials and Methods In this retrospective study, conducted between October 2019 and September 2020, coronary vessels in patients with stable chest pain and with intermediate probability of coronary artery disease who underwent both CCTA and PET MPI with oxygen 15-labeled water or nitrogen 13 ammonia and quantification of myocardial blood flow were analyzed. CCTA images were used in assessing stenosis severity, lesion-specific total plaque volume (PV), noncalcified PV, calcified PV, and plaque phenotype. PET MPI was used in assessing significant coronary stenosis. The predictive performance of the CCTA-derived parameters was evaluated by using area under the receiver operating characteristic curve (AUC) analysis. Results There were 92 coronary vessels evaluated in 53 patients (mean age, 65 years ± 7; 31 men). ESS was higher in lesions with greater than 50% stenosis versus those without significant stenosis (mean, 15.1 Pa ± 30 vs 4.6 Pa ± 4 vs 3.3 Pa ± 3; P = .004). ESS was higher in functionally significant versus nonsignificant lesions (median, 7 Pa [interquartile range, 5-23 Pa] vs 2.6 Pa [interquartile range, 1.8-5 Pa], respectively; P ≤ .001). Adding ESS to stenosis severity improved prediction (change in AUC, 0.10; 95% CI: 0.04, 0.17; P = .002) for functionally significant lesions. Conclusion The combination of endothelial shear stress with coronary CT angiography (CCTA) stenosis severity improved prediction of an abnormal PET myocardial perfusion imaging result versus CCTA stenosis severity alone. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kusmirek and Wieben in this issue.

Fluorine-18 fluorodeoxyglucose positron emission tomography-based textural features for prediction of event prone carotid atherosclerotic plaques.

BACKGROUND: Texture analysis has been increasingly used in the field of positron emission tomography (PET)/computed tomography (CT) imaging with Fluorine-18 fluorodeoxyglucose (18F-FDG), aiming at assessing tumor heterogeneity. The purpose of the present study is to examine the feasibility of performing texture analysis in carotid arteries, investigate the value of textural features as predictors of potential plaque vulnerability using as reference standards histological and immunohistochemical data and compare their performance with conventional uptake measurements. METHODS: 67 different 18F-FDG PET-based textural features were extracted from carotid images of 21 patients with high-grade carotid stenosis undergoing endarterectomy. To identify the more reliable predictors, univariate logistic regression analysis was performed. The accuracy was satisfactory in case of an Area Under the Receiver Operating Characteristic (ROC) curve (AUC) ≥ 0.80. RESULTS: First measure of information correlation (AUC = 0.87, P < 0.001), large zone low gray level emphasis (AUC = 0.87, P < 0.001), and normalized run length non-uniformity (AUC = 0.84, P < 0.001) were the most optimal textural features for identifying characteristics of plaque vulnerability based on histological analysis. Addition of textural features to target-to-background ratio (TBR) (AUC = 0.74, P = 0.031) resulted in an AUC = 0.92 (P < 0.001), however, this did not reach statistical significance (Pdiff = 0.09). Intensity histogram standard deviation (AUC = 0.87, P < 0.001) and joint variance (AUC = 0.81, P = 0.001) were the most efficient features for signal differential in relation to immunohistochemical findings and provided incremental value compared to TBR (Pdiff = 0.02). CONCLUSION: Texture analysis can be applied in 18F-FDG PET carotid imaging providing valuable information for plaque characterization.

Fluid Dynamics-Derived Parameters in Coronary Vessels.

Continued development in the field of cardiovascular modeling over the past few years has contributed to the production of precise three-dimensional models of main coronary arteries. Computational fluid dynamic-derived parameters such as smartFFR, a CT-FFR surrogate, and endothelial shear stress (ESS) can be assessed from non-invasive imaging techniques like computed tomography coronary angiography using novel 3D reconstruction methods and can be used to investigate the functional significance of an artery. The investigation of the different flow conditions for the calculation (steady state vs. transient) of the ESS presents that while there is a difference in the final values, it is not statistically significant. ESS in the whole vessel is higher compared to the lesion-specific segments and smartFFR calculated in lesion segment does not reflect accurately the flow capability of the vessel. Higher ESS is present in vessels with <0.85 smartFFR and both parameters are present higher values in vessels with abnormal PET myocardial perfusion imaging.

Nuclear Cardiology practice in COVID-19 era.

The Coronavirus Disease 2019 (COVID-19) pandemic is the biggest shock in decades to the well developed healthcare system and resources worldwide. Although there was a wide variation in the level of preparedness, the transition was tough even for the most renowned healthcare systems. Increasing the capacity and adapting healthcare for the needs of COVID-19 patients is described by the WHO as a fundamental outbreak response measure. However, while the system is preoccupied with a pandemic infection, patients suffering from other illnesses are in high risk to get infected, also being compromised by the imperative shift in medical resources and significant restrictions on routine medical care. For example patients with cardiovascular disease and others referred for nuclear cardiology procedures are frequently greater than 60 years of age and have other comorbidities (e.g. hypertension, diabetes, chronic lung disease, and chronic renal disease) that place them at a high-risk for adverse outcomes with COVID-19, providing unique challenges for their management in healthcare facilities, as well as for the care of health care personnel. Numerous medical specialty societies and governmental agencies issued guidelines aiming at the specification of preventive measures and amendments in everyday clinical practice during the escalation and peak of the pandemic. In accordance, the American Society of Nuclear Cardiology (ASNC) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI), issued a common statement in late March 2020, which was provided as an initial response to this pandemic, offering specific recommendations for adapting nuclear cardiology practices at each step in a patient's journey through the lab-for inpatients, outpatients and emergency department patients. One of the main recommendations was cancelling or delaying of all non-urgent nuclear cardiology studies. As COVID-19 follows a different time course in different geographic regions and lockdowns begin to lift in many countries, the issue of re-establishment of non-emergent care, in nuclear cardiology laboratories amongst others, has to be addressed in a watchful and balanced way, keeping in mind that the COVID-19 crisis is far from over. Furthermore measuring what is happening in the current crisis is essential to ensuring preparedness for a possible next wave of the pandemic. Recently the ASNC, SNMMI, the International Atomic Energy Agency (IAEA) and the Infectious Disease Society of America (IDSA), issued an information statement which describes a careful approach to reestablishment of non-emergent care in nuclear cardiology laboratories reflecting diverse settings from the United States and worldwide. In the same spirit it is also the reintroduction guidance issued by North American Cardiovascular Societies. In this paper we provide a synopsis of the basic steps of adapting nuclear cardiology practice in the era of COVID-19 in order to balance between the risk of viral transmission while also providing crucial cardiovascular assessments for our patients.

Noninvasive CT-based hemodynamic assessment of coronary lesions derived from fast computational analysis: a comparison against fractional flow reserve.

OBJECTIVES: Application of computational fluid dynamics (CFD) to three-dimensional CTCA datasets has been shown to provide accurate assessment of the hemodynamic significance of a coronary lesion. We aim to test the feasibility of calculating a novel CTCA-based virtual functional assessment index (vFAI) of coronary stenoses > 30% and ≤ 90% by using an automated in-house-developed software and to evaluate its efficacy as compared to the invasively measured fractional flow reserve (FFR). METHODS AND RESULTS: In 63 patients with chest pain symptoms and intermediate (20-90%) pre-test likelihood of coronary artery disease undergoing CTCA and invasive coronary angiography with FFR measurement, vFAI calculations were performed after 3D reconstruction of the coronary vessels and flow simulations using the finite element method. A total of 74 vessels were analyzed. Mean CTCA processing time was 25(± 10) min. There was a strong correlation between vFAI and FFR, (R = 0.93, p < 0.001) and a very good agreement between the two parameters by the Bland-Altman method of analysis. The mean difference of measurements from the two methods was 0.03 (SD = 0.033), indicating a small systematic overestimation of the FFR by vFAI. Using a receiver-operating characteristic curve analysis, the optimal vFAI cutoff value for identifying an FFR threshold of ≤ 0.8 was ≤ 0.82 (95% CI 0.81 to 0.88). CONCLUSIONS: vFAI can be effectively derived from the application of computational fluid dynamics to three-dimensional CTCA datasets. In patients with coronary stenosis severity > 30% and ≤ 90%, vFAI performs well against FFR and may efficiently distinguish between hemodynamically significant from non-significant lesions. KEY POINTS: Virtual functional assessment index (vFAI) can be effectively derived from 3D CTCA datasets. In patients with coronary stenoses severity > 30% and ≤ 90%, vFAI performs well against FFR. vFAI may efficiently distinguish between functionally significant from non-significant lesions.

Cardiovascular preclinical imaging.

Non-invasive imaging in the form of single-photon emission-computed tomography (SPECT), positron-emission tomography (PET), computed tomography (CT), echocardiography or magnetic resonance imaging (MRI) is a very useful tool for cardiovascular research as it allows assessment of biological processes in vivo. Nuclear imaging with SPECT and PET offers the advantage of high sensitivity, the potential for serial imaging, and reliable quantification. Currently a wide range of established as well as innovative agents is available and can be imaged with dedicated preclinical and clinical SPECT and PET imaging systems. These scanners can be equipped with CT and MRI components to form hybrid imaging systems. This review provides an outline on SPECT and PET as capable tools for translational research in cardiology as part of a workflow similar to the one used in clinical imaging illustrating the concept "from bench to bedside".

One Coin, No Need to Flip: Shared PET Targets in Cancer and Coronary Artery Disease.

OBJECTIVE: The purposes of this article are to review the common biologic features of cancer and coronary artery disease assessed with PET tracers, focusing on those already used in the clinic and those with translational potential, and to discuss the current value and expected contribution of PET in diagnosis, risk stratification, and treatment monitoring. CONCLUSION: PET using a wide variety of radiotracers enhances understanding of pathophysiologic changes shared by cancer and coronary artery disease, helps establish an accurate diagnosis, and aids in prognostic assessment and management decisions. It is likely that with the evolution of therapeutic strategies for blocking the development and progression of both diseases and with the introduction of novel, specific ligands in clinical practice, PET will play an ever stronger role in diagnosis, risk stratification, and monitoring of therapy.

Central nervous system disorders affecting the heart-insights from radionuclide imaging.

There is a growing research activity focusing on the brain heart cross-talk. A great variety of brain disorders affect the heart and recent developments in neurosciences have revealed the particular role of specific neuroanatomic sites on heart rhythm and rate, myocardial function and vascular tone. Cardiac radionuclide imaging plays a pivotal role in this setting, since not only helps elucidating underlying pathobiological mechanisms but in addition, it promises exciting possibilities for early identification of patients at risk of developing cardiovascular manifestations of certain neurological diseases.

EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT: 2015 revision.

Since the publication of the European Association of Nuclear Medicine (EANM) procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in 2005, many small and some larger steps of progress have been made, improving MPI procedures. In this paper, the major changes from the updated 2015 procedural guidelines are highlighted, focusing on the important changes related to new instrumentation with improved image information and the possibility to reduce radiation exposure, which is further discussed in relation to the recent developments of new International Commission on Radiological Protection (ICRP) models. Introduction of the selective coronary vasodilator regadenoson and the use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography are other important areas for nuclear cardiology that were not included in the previous guidelines. A large number of minor changes have been described in more detail in the fully revised version available at the EANM home page: http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_guideline.pdf .

Cardiac PET for translational imaging.

All along, translational cardiovascular research has been dependent on non-invasive imaging (such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), echocardiography, or magnetic resonance imaging (MRI)), as these techniques allow the assessment of surrogate markers in intact living organisms non-invasively. PET offers the advantages of high sensitivity; the capability for longitudinal, quantitative imaging; and that an armamentarium of promising radiotracers is readily available. All commercially available PET scanners are equipped with a CT component, and thus, the often cited disadvantage of a lack of morphologic correlation does not really count anymore. This review aims to give an outline on PET as a promising tool for translational research in cardiology as dedicated preclinical systems with virtually the same imaging features as those used in clinical imaging allows the straightforward concept of "bench to bedside."

Effects of cigarette smoke exposure and its cessation on body weight, food intake and circulating leptin, and ghrelin levels in the rat.

INTRODUCTION: Smoking is associated with loss of body weight (BW) and reduced appetite, while smoking abstinence with the opposite effect. The role of peripheral signaling by appetite-controlling hormones leptin and ghrelin is not clear. In the present study, the relationship of circulating leptin and ghrelin with BW and food intake rate (FIR) changes was studied during cigarette smoke exposure (CSE) and after its cessation in the rat. METHODS: Male Wistar rats were subjected to CSE for 8 weeks by confinement to plexiglass chambers (Group S). Control animals were confined to identical chambers without smoke (Group C). During CSE and an equivalent follow-up period, BW and FIR was recorded and serum leptin and ghrelin levels were measured. RESULTS: A sharp decrease in BW was noted during the first 4 weeks of CSE, while FIR, after a substantial decrease noted at Week 1, returned to control levels. Thereafter, rats started to regain their BW until they reached control levels by the 1st week postCSE. BW regain was accompanied by a rebound increase of FIR, which plateaued during the first 4 weeks postCSE and then normalized. Serum leptin was decreased in Group S during both periods, normalizing at the 7th week postCSE. Ghrelin levels did not differ between groups. CONCLUSIONS: Circulating leptin could not explain by its own BW and FIR changes during the first few week of CSE in rats, in contrast to the rest of the CSE period as well as after its cessation. Serum ghrelin levels did not justify BW and FIR changes.