Hemodynamic and Neurohumoral responses to acute hypovolemia in conscious mammals

By: James C. Schadt and John Ludbrook (Dalton Research Center and Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211; and Cardiovascular Research Laboratory, Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia)

During the initial studies on hemorrhage, two phases of hemodynamic responses were observed. The first being peripheral resistance and heart rate(HR) increases to compensate for the fall in cardiac output (CO). The second phase involves vasodilation, as opposed to vasoconstriction in phase 1, which is combined with bradycardia, which will cause blood pressure (BP) to drop. Phase 1 has also shown to have an increase in sympathetic nerve activity (SNA). Important contributors to this entire process are the baroreceptors and the receptors in cardiopulmonary regions. They are important for sensing the hemodynamic changes that occur on a beat to beat basis. This information is then relayed to the brain, which will then cause the vasoconstriction in phase 1, followed by vasodilation in phase 2.

Phase 1 features sympathoexcitation, which is the cause of the constricting blood vessels. This process lasts until blood loss exceeds 25-35% of blood volume. The process compensates for the drop in blood volume so that the arterial pressure doesn't fall with it. Norepinephrine (NE) is seen as the major contributor to the constricting blood vessels. This was proven by giving an alpha 1 adrenoceptor blocker, which prevented the blood vessels from constricting. HR is the second factor in phase 1, but does not contribute as much. The rise in CO during tachycardia is not enough to maintain the blood volume. Plasma renin activity also has been shown to rise during phase 1. This also helps in counteracting the fall in BP by increasing peripheral resistance.

When studying the baroreceptor, sinoaortic barodenervation (SAD) was used to prove what type of control the baroreceptor had on hemodynamic responses. During chronic SAD, the responses that occur in phase 1 were abolished, which prevented the ability to compensate for the blood loss. This study was important to show that the afferents are vital to sense the changes that are occurring, which will then signal the body to react.

Phase 2 involves a drop in blood volume and BP passed a critical point that the body is not able to compensate. HR decreases with a decrease in BP. CO is unrelated to the onset of hypotension in this phase. The fall in BP is due to a drop in peripheral resistance. SNA is decreased followed by an increase in vasodilation.

Opioids have also seen to affect acute hemorrhagic hypotension. Naloxone increases BP during a hemorrhage. During normal conditions, it does not have the same affect. This could mean that mechanisms that are antagonized by naloxone are inactive in normal conditions.

I probably should've read this review before I read the experimental studies, but this paper does a great job summarizing the different mechanisms and effects that take place during a hemorrhage. I will use this information during my experiments to visualize what is mentioned on paper, in a real life setting.

-Tsetse Fly