Vasodilators in critical illness

Vasodilators are commonly used in the intensive care unit (ICU) to control arterial blood pressure, unload the left or the right heart, control pulmonary artery pressure, and improve microcirculatory blood flow. Vasodilator refers to drugs acting directly on the smooth muscles of peripheral vessel walls and drugs are usually classified based on their mechanism (acting directly or indirectly) or site of action (arterial or venous vasodilator). Drugs that have a predominant effect on resistance vessels are arterial dilators and drugs that primarily affect venous capacitance vessels are venous dilators. Drugs that interfere with sympathetic nervous system, block renin-angiotensin system, phosphodiesterase inhibitors, and nitrates are some examples of drugs with indirect effect. Vasodilator drugs play a major therapeutic role in hypertensive emergencies, primary and secondary pulmonary hypertension, acute left heart, and circulatory shock. This review discusses the main types of vasodilators drugs commonly used in the ICU.

MECHANICAL CHARACTERISTICS OF CORONARY CIRCULATION

The phase opposition of velocity waveforms between coronary arteries (predominantly diastolic) and veins (systolic) is the most prominent characteristic of coronary hemodynamics. The phase opposition indicates the importance of intramyocardial capacitance vessels, as a determinant of phasic coronary arterial and venous flows. To investigate the functional characteristics of the intramyocardial capacitance vessels and its physiological significance, we analyzed the change in venous flow following changes in coronary arterial inflow. It was shown that during diastole the intramyocardial capacitance vessels have two functional components, unstressed volume and ordinary capacitance. Unstressed volume is defined as the volume of blood in a vessel at zero transmural pressure, and it was ~5% of the volume of the myocardium. The systolic coronary venous outflow showed a significant, positive correlation with the total displaceable blood volume stored in the intramyocardial unstressed volume and ordinary capacitance. When the unstressed volume was saturated, the coronary inflow was decreased significantly, compared with that for the unsaturated condition. Thus, the increase in intramyocardial blood volume decreases the coronary arterial inflow, whereas it enhances coronary venous outflow. The latter is an interesting analogy to the Starling's law of the heart.

Cardiovascular effects of vasopressin following V1 receptor blockade compared to effects of nitroglycerin

Studies to more clearly determine the mechanisms associated with arginine vasopressin (AVP)-induced vasodilation were performed in normal subjects and in quadriplegic subjects with impaired efferent sympathetic responses. Studies to compare the effects of AVP with the hemodynamic effects of nitroglycerin, an agent that primarily affects venous capacitance vessels, were also performed in normal subjects. Incremental infusions of AVP following V1-receptor blockade resulted in equivalent reductions in systemic vascular resistance (SVRI) in normal and in quadriplegic subjects. However, there were major differences in the effect on mean arterial pressure (MAP), which was reduced in quadriplegic subjects but did not change in normal subjects. This difference in MAP can be attributed to a difference in the magnitude of increase in cardiac output (CI), which was twofold greater in normal than in quadriplegic subjects. These observations are consistent with AVP-induced vasodilation of arterial resistance vessels with reflex sympathetic enhancement of CI and are clearly different from the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and indexes of cardiac preload, with only minor changes in SVRI.