Cardiovascular Physiology and Pharmacology Flashcards

A 65-year-old male with severe biventricular heart failure is receiving an intravenous infusion of milrinone. What is the primary mechanism of action responsible for its inotropic and vasodilatory effects?

Answer: Inhibition of phosphodiesterase-3 (PDE3), leading to increased intracellular cAMP.

Milrinone is a phosphodiesterase-3 (PDE3) inhibitor. By inhibiting PDE3, it prevents the breakdown of cyclic adenosine monophosphate (cAMP) in both cardiac myocytes and vascular smooth muscle. The resulting increase in intracellular cAMP in the heart leads to enhanced calcium influx and a positive inotropic effect (increased contractility). In the vascular smooth muscle, increased cAMP promotes relaxation, leading to both arterial and venous vasodilation, which reduces afterload and preload.

During a rapid intravenous fluid bolus in a healthy, euvolemic patient, an increase in heart rate is observed despite a minimal change in arterial blood pressure. Which physiological reflex is predominantly responsible for this tachycardia?

Answer: Bainbridge reflex (atrial reflex)

The Bainbridge reflex, or atrial reflex, is triggered by an increase in central venous pressure and stretching of the atrial walls, which occurs during rapid volume infusion. Stretch receptors in the atria send signals via vagal afferents to the medulla, leading to an inhibition of parasympathetic output and a subsequent increase in heart rate. This reflex helps to prevent venous congestion by increasing cardiac output to handle the increased venous return. The baroreceptor reflex would be expected to decrease the heart rate in response to an increase in blood pressure.

A patient undergoing cardiac surgery has an aortic diastolic pressure of 70 mmHg and a left ventricular end-diastolic pressure (LVEDP) of 20 mmHg. What is the calculated coronary perfusion pressure (CPP) for the left ventricle?

Answer: 50 mmHg

The left ventricle is perfused almost exclusively during diastole because the high intra-myocardial pressure during systole compresses the coronary vessels. Therefore, the coronary perfusion pressure (CPP) for the left ventricle is calculated as the difference between the aortic diastolic pressure (the driving pressure) and the left ventricular end-diastolic pressure (the back pressure or impedance to flow). CPP = Aortic Diastolic Pressure - LVEDP. In this case, CPP = 70 mmHg - 20 mmHg = 50 mmHg.

Which of the following best describes the effect of vasopressin (at therapeutic doses for vasoplegic shock) on systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR)?

Answer: Increases SVR with minimal or no effect on PVR

Vasopressin acts on V1 receptors in vascular smooth muscle to cause potent vasoconstriction, thereby significantly increasing systemic vascular resistance (SVR). However, its effect on the pulmonary vasculature is different. Several studies have shown that vasopressin has minimal to no vasoconstrictive effect on the pulmonary arteries, and it may even cause a relative decrease in the PVR to SVR ratio. This makes it a useful pressor in patients with right ventricular dysfunction or pulmonary hypertension where an increase in PVR would be detrimental.

The administration of a pure positive inotropic agent, such as dobutamine, would cause which of the following changes on a left ventricular pressure-volume (PV) loop, assuming constant preload and afterload?

Answer: An upward and leftward shift of the end-systolic pressure-volume relationship (ESPVR) line.

Positive inotropic agents increase myocardial contractility. On a PV loop, this is represented by an increase in the slope of the end-systolic pressure-volume relationship (ESPVR) and a shift of this line to the left. This means that for any given end-systolic volume, the ventricle can generate more pressure. The loop itself becomes wider (increased stroke volume) and shifts to the left (decreased end-systolic volume) as the heart ejects blood more effectively.

A patient on mechanical ventilation develops acute hypercapnia (PaCO2 increases from 40 mmHg to 65 mmHg) with associated acidosis. What are the expected direct effects on the systemic and pulmonary vasculatures?

Answer: Systemic vasodilation and pulmonary vasoconstriction

Hypercapnic acidosis has opposing effects on the systemic and pulmonary circulations. Systemically, it causes vasodilation, which decreases afterload. In contrast, in the pulmonary vasculature, hypercapnia is a vasoconstrictor, an effect that can augment hypoxic pulmonary vasoconstriction (HPV). This response in the lungs helps to match perfusion to ventilation. The systemic effects are often counteracted by a sympathoadrenal response leading to a net increase in cardiac output, but the direct vascular effect is dilation.