[Regulation of cardiac output;an approximation at 3 levels: organic, cellular, and protein]

Abstract

The heart is the central point for adaptation of the organism to physical exercise because it is the center of the energy support system. Its activity is regulated at three levels; organ, cells and molecular and genetic components. During the development of the heart, the organ adapts in response to chronic and acute overloads by instantaneous functional and chronic changes, leading to a variable degree of cardiac growth. Physical exercise (acute and chronic) is the main example of physiologic overload. The acute response of the heart means a mechanical-hemodynamical and energetic modulation, driving to a final point where oxygen supply fits the increased need. Training, as response to chronic exercise, promotes an increase in energetic capacity (heart rate and stroke volume), structurally reflected in the physiological cardiac hypertrophy. Global functional and structural changes express what is happening at the cellular level. Different stimuli signal through specific receptors and second messengers to the nucleus, regulating gene expression and conditioning structural (size) and functional (contractile) changes. Changes in cellular size explain, by Starling mechanism, the increase in individual contractile strength and in reduction of the ventricular cavity in the systolic period. Other structural changes refer to the interstitium, myocardial vasculature and vascular reactivity. Changes in contractility affect the composition of the contractile elements (isoforms of heavy myosin, light myosin and/or modulatory proteins) and sarcoplasmic Ca2+ regulation, through the increase in Ca2+ flow. Many of the adaptations to chronic exercise studied in vivo in intact heart, isolated heart (Langendorf) or papillary muscle (multicellular preparation), are retained in the cardiomyocyte. Isolated cardiomyocytes can be precisely through the medium, temperature, ionic composition, active substances, etc. Shortening speed without load (Vmax), considered an inotropic index (Sonnenblick) can be measured independently of the initial length. Myocytes shorten against an internal load (restoration force) with viscous and elastic components, although they cannot be loaded externally (stretching is difficult). Cardiomyocyte isolation and maintenance requires strict and controlled conditions. This model offers many possibilities for studying dimensions, contraction-relaxation mechanics, Ca2+ and pH dynamics, beta-adrenergic receptors, electrophysiology, pharmacology, genetics, etc. This kind of studies can deal with normal myocytes or myocytes from trained animals, cardiomyopathies, etc.