Physiopharmacological evaluation of myocardial performance how to study modulation by cardiac endothelium and related humoral factors?

Time for primary review 24 days. When conducting human or animal experiments in a search for an understanding of the regulation and dysfunction of the cardiovascular system, clinicians and scientists have been confronted with the complexity of this system. Although complexity could be studied at any magnification, it has, in general, followed a reductionist approach 1, 2. In this way, by bypassing or eliminating as many interacting processes as possible, our view on cardiac performance has become ever narrower in scope. For example, excluding neurohumoral control and uncoupling the heart from the peripheral circulation reduced our experimental approach from in-situ animal experiments to isolated experimental conditions, as e.g. the Langendorff-perfused heart and various, more recent, modified versions of it, where the heart is no longer necessarily considered as an input–output pump with ventricular filling (end-diastolic pressure and volume) and cardiac output (systolic pressure and stroke volume) as major features. With the heart as a muscular pump and, more specifically, in view of the strongly time-dependent activation and inactivation processes, time became inherent in any consideration concerning the performance, regardless of the hierarchic level at which it is being studied. Next, attempts to eliminate the complex dynamic architecture of the intact heart have led to the usage of isolated papillary muscles. This allowed cardiac physiologists to apply technology and principles from skeletal muscle physiology, with the addition of the dimension of time through close analysis of twitches, instead of tetani. Isolated single cardiomyocytes were introduced to bypass multicellularity and nonuniform behavior (damaged ends); nonuniformity being evidenced, in multicellular cardiac muscle preparations, by laser diffraction methods 3or by segmental analysis 4, 5. In single cardiomyocytes, techniques were developed to bypass the natural membrane-linked activation processes, e.g. by (hyper)permeabilizing the cardiomyocytes 6, 7, or to eliminate cytoplasmic activation control, … * Corresponding address: Tel.: +32 3 218 02 77; Fax: +32 3 218 02 76; E-mail: stsys@ruca.ua.ac.be