Cough response in specific pathogen-free guinea pig animal model.

Laboratory animal science associations recommend the usage of specific pathogen-free (SPF) animals in experiments to achieve appropriate results. However, their non-natural microbiome might represent an obstacle in the successful translation of obtained results into clinical practice, since the microbiome contributes to the regulation of the host's physiology. Inconsistent results, even in repeated experiments in separate animal groups, irrespective of the season or sex led us to assess the cough response of SPF animal variables and compare it to wild-type animals. The dose-response curves in citric acid and capsaicin cough challenge construction shows significantly increased cough threshold in SPF animals compared to wild-type animals of both sexes. The cause of cough response alteration in SPF animals is not presently known and thus their usage in basic cough research remains questionable. The relationship between airway reflexes and the airway microbiome has never been studied hence we propose that it might be microbiome-related.

Modification of oestrogen signalling pathways influences cough induced by citric acid but not capsaicin in the animal model of both sexes.

To clarify the role of oestrogen signalling and the role of oestrogen receptor alpha (ERα) in the cough pathways we performed a study in which coughing was observed in both sexes animal models after the treatment by selective ERα degrader fulvestrant (ICI 182-780) and inhibitor of oestrogen synthesis danazol. Degradation of ERα with the normal plasma oestrogen levels induced by fulvestrant, significantly augments the cough response of female but not male guinea pigs. These changes were observed in citric acid-induced cough. Female guinea pigs responded with an increased count of cough expulsions per challenge time and we also detected shorter cough latency. The capsaicin-induced cough did not change. A similar response was observed after danazol treatment, which decreased the plasma oestrogen level. Our results indicate that the transient receptor potential vanilloid-1 (TRPV1) channel-mediated cough is resistant to the hypoestrous state, while the citric acid-mediated cough is oestrogen-dependent and hypersensitive during the hypoestrous state.

Animal models of cough.

Cough is a vital airway reflex that keeps the respiratory tract wisely protected. It is also a sign of many diseases of the respiratory system and it may become a disease in its own right. Even though the efficacy of antitussive compounds is extensively studied in animal models with promising results, the treatment of pathological cough in humans is insufficient at the moment. The limited translational potential of animal models used to study cough causes, mechanisms and possible therapeutic targets stems from multiple sources. First of all, cough induced in the laboratory by mechanical or chemical stimuli is far from natural cough present in human disease. The main objective of this review is to provide a comprehensive summary of animal models currently used in cough research and to address their advantages and disadvantages. We also want to encourage cough researchers to call for precision is research by addressing the sex bias which has existed in basic cough research for decades and discuss the role of specific pathogen-free (SPF) animals.

Acute consciousness disorders in intensive care medicine - value of its grading for prognostic conclusion.

OBJECTIVES: To understand consciousness we have to understand the mechanism of its function, which is to effectively organize sensory inputs from our environment. Consciousness is the basic, essential outcome of the process of organizing these sensory inputs, resulting in cognitive, mental, emotional, executive, instinctual or other marginally aware states. This reciprocal process of the CNS implies that organization is an act, which precedes consciousness, i.e. preconscious function. Most scientific explanations portray consciousness as an "emergent property" of classical computer-like activities in the brains neural networks. Doctors at ICU work daily with patients with altered human consciousness. Therefore, they must recognize and manage it skilfully and use adequate approaches for definite solutions. MATERIAL AND METHODS: We observed a series of patients with traumatic and non traumatic brain injuries admitted to the ICU. The quality of life of these patients during the course of intensive care was very elementary and the final outcome GCS (oGCS) for future life was defined as a comatose state or apallic state, very rarely was it restored to premorbid condition as far as lucidity, attention, cognition, and executive functions. RESULTS: We found that a significant oGCS increase in relation to condition at admission or intake GCS (iGCS) in the group with 184 patients total (p<0.00001), in cardio-pulmonary resuscitation (CPR), traumatic brain injury (TBI) subgroups (p<0.00001) and in spontaneous haemorrhage (SH) (p<0.05) represents the only basic prerequisite for further improvement. It is not easy to find good therapeutic approaches after traumatic and non traumatic brain injury. A statistically significant oGCS increase in relation to iGCS due to quite intense medical care and keeping disclosed the state of unconsciousness with further probable evolution through the following possible ways: death in fluent comatose state, delirium and awakening, delirium ending in death, direct awakening from comatose state. Therefore significantly increased oGCS is the only basic prerequisite for pragmatically optimal "quality of life" in the course of later life. CONCLUSION: We raise general questions for both scientists and clinicians that will assist in their efforts to understand the basic endogenous conscious biological processes, their pathological changes and the links between them.

Surgical management of the aortic root in patients with Marfan syndrome.

BACKGROUND AND AIM OF THE STUDY: Surgical aortic root reconstruction techniques are standard therapy to avoid catastrophic vascular events in patients with Marfan syndrome with a dilated and/or dissected aortic root. The study aim was to evaluate the long-term results of aortic root reconstruction. METHODS: Eighty-three patients (54 males, 29 females; mean age 37+/-17 years) fulfilling strict Ghent criteria for Marfan syndrome underwent aortic root surgery between 1971 and 2001. Of these patients, 65 (78%) underwent a composite valve conduit repair and 18 (22%) a valve-sparing aortic root reconstruction. Six patients (7%) suffered from an acute type A dissection, and 16 (19%) a chronic type A dissection. RESULTS: In-hospital and 30-day mortality was 3.6% (n = 3). Morbidity included stroke (1.2%; n = 1), perioperative myocardial infarction (1.2%; n = 1) and reoperation for bleeding (10%; n = 8). Of 21 late deaths, the cause was cardiac in nine cases. Actuarial survival at 5, 10, 15 and 20 years was 84% (95% CI 76-93%), 73% (CI 61-86%), 59% (CI 45-77%) and 43% (CI 26-72%), respectively. Multivariate predictors for late death were postoperative dysrhythmias and need for inotropes (p < or =0.01). Freedom from reoperation at 5, 10, 15 and 20 years was 86% (CI 78-95%), 69% (CI 56-85%), 53% (CI 38-74%) and 48% (CI 23-71%), respectively. Multivariate predictors for reoperation were preoperative mitral valve prolapse and an initial valve-sparing aortic procedure (p < or =0.05). In the composite valve conduit patients, freedom from thromboembolism was 88% (CI 76-100%), and from endocarditis was 99% (CI 93-100%) at 15 years. CONCLUSION: Composite valve conduit replacement of the aortic root in patients with Marfan syndrome offers a durable result, with low mortality and long-term complication rates. Reoperation was most commonly required for cardiac and vascular disease unrelated to the initial operation and in patients undergoing a valve-sparing aortic root procedure.

Surgery for aneurysms of the aortic root: a 30-year experience.

BACKGROUND: This study evaluated long-term results of aortic root replacement and valve-preserving aortic root reconstruction for patients with aneurysms involving the aortic root. METHODS AND RESULTS: Two-hundred three patients aged 53+/-16 years (mean+/-SD; 153 male, 50 female) underwent elective or urgent aortic root surgery from 1971 to 2000 for an aortic root aneurysm: 149 patients underwent a composite valve conduit reconstruction, and 54 patients underwent valve-preserving aortic root reconstruction. Fifty patients had Marfan syndrome. In-hospital and 30-day mortality was 4.0% (8/203) overall: for a composite valve conduit procedure, the corresponding value was 4.0% (6/149) and for valve-preserving procedure, 3.7% (2/54) (P=NS). Morbidity included 3 strokes (1%), 10 perioperative myocardial infarctions (5%), and 8 reoperations for bleeding (4%). Actuarial survival at 5, 10, 15, and 20 years was 93% (95% confidence interval [CI] = 88% to 97%), 79% (95% CI = 71% to 87%), 67% (95% CI = 57% to 79%), and 52% (95% CI = 36% to 69%), respectively. Freedom from reoperation was 72% (95% CI = 54% to 86%) at 20 years. Complications with anticoagulation occurred in 29 patients; with valve thrombosis, in 2; and with hemorrhage, in 27 (4 life threatening and 23 minor). Freedom from thromboembolism was 91% (95% CI = 77% to 98%) at 20 years. Freedom from endocarditis was 99% (95% CI = 92% to 100%) at 20 years. Multivariate analysis revealed preoperative mitral valve regurgitation (+3 to 4) and older age to be significant predictors of late death (P< or =0.005), and Marfan syndrome, initial valve-preserving aortic root reconstruction, and need for a concomitant procedure at initial operation to be significant predictors of the need for reoperation (P< or =0.01). CONCLUSIONS: Aortic root replacement for aortic root aneurysms can be done with low morbidity and mortality. Composite valve conduit reconstruction resulted in a durable result. There were few serious complications related to the need for long-term anticoagulation or a prosthetic valve. Reoperation was most commonly required because of failure of the aortic valve when a valve-preserving aortic root reconstruction was performed or for other cardiac or aortic disease elsewhere.