Within the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs.

Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics.

This paper presents a method for breath-by-breath noninvasive estimation of respiratory resistance and elastance in mechanically ventilated patients. For passive patients, well-established approaches exist. However, when patients are breathing spontaneously, taking into account the diaphragmatic effort in the estimation process is still an open challenge. Mechanical ventilators require maneuvers to obtain reliable estimates for respiratory mechanics parameters. Such maneuvers interfere with the desired ventilation pattern to be delivered to the patient. Alternatively, invasive procedures are needed. The method presented in this paper is a noninvasive way requiring only measurements of airway pressure and flow that are routinely available for ventilated patients. It is based on a first-order single-compartment model of the respiratory system, from which a cost function is constructed as the sum of squared errors between model-based airway pressure predictions and actual measurements. Physiological considerations are translated into mathematical constraints that restrict the space of feasible solutions and make the resulting optimization problem strictly convex. Existing quadratic programming techniques are used to efficiently find the minimizing solution, which yields an estimate of the respiratory system resistance and elastance. The method is illustrated via numerical examples and experimental data from animal tests. Results show that taking into account the patient effort consistently improves the estimation of respiratory mechanics. The method is suitable for real-time patient monitoring, providing clinicians with noninvasive measurements that could be used for diagnosis and therapy optimization.