The principal function of the cardiovascular (CV) system is to deliver oxygen and nutrients to and remove carbon dioxide and wastes from metabolizing tissues. This is accomplished by means of two specialized circulations in series: a low-resistance pulmonary and a high-resistance systemic circulation driven by specialized muscle pumps, the right and left heart (each in turn composed of a thin-walled atrium and thicker-walled ventricle), respectively. Although CV physiology can be understood at a number of hierarchical levels, the complex interplay among the intrinsic properties of the cardiomyocytes and isolated muscle, chamber mechanics, and their modulation by variable cardiac-loading conditions and neurohormonal and renal compensatory mechanisms determines the integrated performance of the CV system. Accordingly, CV physiology will be examined at cellular, isolated muscle, and organ (isolated heart and integrated systems) levels.
Excitation: The Action Potential
The rhythmic beating of the heart distinguishes it from all other organs. The normal heartbeat is initiated by a complex flow of electrical signals called action potentials. The action potential results from highly coordinated, sequential changes in ion conductances through gated sarcolemmal membrane channels (Fig. 5–1).
Phases of the action potential and major associated currents in ventricular myocytes. The initial phase 0 spike is not labeled. See discussion of excitation in text. In specialized conduction system tissue, there is spontaneous depolarization during phase IV. Ca2+, calcium; K+, potassium; Na+, sodium. Reproduced with permission from LeWinter MM, Osol G. Normal physiology of the cardiovascular system. In: Fuster V, Alexander RW, O'Rourke RA, Roberts R, et al, eds. Hurst's The Heart. 11th ed. New York: McGraw-Hill, 2004:87-112.
Increases in transmembrane potential from a resting value of −80 to −90 mV to approximately +30 mV (depolarization) represents phase 0 (the rapid upstroke) of the action potential and results primarily from a sudden increase in sodium (Na+) permeability; this permits a large inward current of Na+ ions to flow down an electrochemical gradient by means of voltage-and time-dependent fast Na+ channels. The upstroke is caused by a regenerative process, that is, depolarization leads to Na+ influx, which leads to further depolarization. The rapid opening of the activation gates for the fast Na+ channel is immediately followed by a slower closing of inactivation gates, which interrupts the influx of Na+ into the cell. The membrane must be fully repolarized for inactivation gates to reopen and conduct another action potential, a process called recovery.
Phase I (the notch) is the initial rapid repolarization phase of the action potential, which is carried by potassium (K+) and to a lesser extent, chloride (Cl−) ion conductance. Phase II of the action potential is unique to cardiac muscle; this plateau phase results from a balance of inward calcium (Ca2+...