Cardiovascular Physiology and Pharmacology Flashcards

A patient with severe aortic stenosis undergoes spinal anaesthesia. Despite a 1.5 L crystalloid pre-load, blood pressure drops to 70/40 mmHg. Phenylephrine is given but cardiac output falls further. Which physiological explanation best accounts for this deterioration?

Answer: Phenylephrine caused reflex bradycardia, reducing diastolic filling time and worsening subendocardial ischaemia in the hypertrophied ventricle

In severe aortic stenosis, the left ventricle is concentrically hypertrophied and heavily dependent on heart rate for cardiac output (CO = HR × SV). Phenylephrine's pure α1-agonism reliably causes baroreceptor-mediated reflex bradycardia. In a fixed-output state with a stiff, non-compliant ventricle, the resulting bradycardia dramatically reduces CO. Additionally, slower heart rate prolongs systole proportionally more than diastole at lower rates, impairing subendocardial perfusion in a hypertrophied myocardium with elevated end-diastolic pressure. Ephedrine or metaraminol (which preserve or increase HR) are preferred vasopressors in this context.

In a patient receiving milrinone for decompensated heart failure, plasma levels of the drug are therapeutic yet the inotropic effect appears diminished compared to initiation. Which molecular mechanism best explains tachyphylaxis to milrinone over 72 hours?

Answer: Upregulation of phosphodiesterase-3 (PDE3) enzyme expression, accelerating cAMP degradation and blunting the net cAMP rise

Sustained PDE3 inhibition by milrinone triggers compensatory upregulation of PDE3 enzyme expression — a well-documented genomic adaptation to chronically elevated cAMP. This increases the cell's cAMP-degrading capacity, partially offsetting milrinone's effect without requiring any change in receptor density. While β1-adrenoceptor downregulation (option A) does occur in chronic heart failure, it is a pre-existing feature rather than a response to milrinone specifically. Option D describes a mechanism relevant to β-agonist tolerance via G-protein–coupled receptor kinase (GRK) phosphorylation, which does not apply to a PDE inhibitor that acts downstream of the receptor.

During cardiopulmonary bypass at 28°C, a patient's arterial pH is 7.52 and PaCO₂ is 29 mmHg when measured at 37°C in the blood gas analyser. Using alpha-stat management, the perfusionist makes no adjustment. Which statement correctly describes the in vivo acid-base status at 28°C?

Answer: The patient is actually eucapnic in vivo; CO₂ becomes more soluble at 28°C, so the true in vivo PaCO₂ is higher than the 37°C measurement, normalising pH to ~7.40

This is the core of alpha-stat vs. pH-stat controversy. CO₂ is more soluble in blood at lower temperatures. When blood cooled to 28°C is warmed to 37°C for analysis, dissolved CO₂ comes out of solution, so the analyser reads a LOWER PaCO₂ than actually exists in the patient at 28°C. Therefore, the true in vivo PaCO₂ at 28°C is higher (closer to 40 mmHg), and pH is closer to 7.40 than the 7.52 measured at 37°C. Alpha-stat management accepts the 37°C measurement as the management target, maintaining constant protein (histidine imidazole) ionisation state across temperatures. The patient is therefore eucapnic in vivo — the apparent alkalosis is a measurement artefact of warming.

A 58-year-old patient with long-standing hypertension is receiving labetalol infusion post-operatively. Despite adequate doses, blood pressure control is poor. Genotyping reveals a CYP2D6 ultra-rapid metaboliser phenotype. Which additional pharmacodynamic complication is most likely to occur specifically because of this genotype?

Answer: Enhanced reflex tachycardia because labetalol's β-blocking effect is lost faster than its α-blocking effect, creating a window of pure α-antagonism with compensatory sympathetic activation

Labetalol is a racemic mixture: the RR-enantiomer provides β1/β2-blockade and the SR-enantiomer provides α1-blockade, with an approximate β:α ratio of 7:1 in the racemic mixture. CYP2D6 is primarily responsible for β-blocking enantiomer metabolism. In ultra-rapid metabolisers, the β-blocking component is cleared disproportionately faster than the α-blocking component (which relies more on glucuronidation). This creates a window where residual α1-blockade reduces SVR, triggering baroreceptor-mediated reflex tachycardia unopposed by β-blockade — a haemodynamically problematic pattern. Dihydrolabetalol (option C) is a real minor metabolite but does not have clinically significant β2-agonist activity.

Which haemodynamic profile is most consistent with acute severe mitral regurgitation (MR) caused by papillary muscle rupture 48 hours post-STEMI, as would be seen on pulmonary artery catheter measurements?

Answer: High PCWP with large V-waves, low cardiac output, high SVR, and elevated right atrial pressure

Acute severe MR from papillary muscle rupture produces a characteristic constellation: (1) Very high PCWP with prominent V-waves — the regurgitant volume is ejected into a non-compliant, unprepared left atrium causing tall V-waves on the wedge tracing; (2) Low forward cardiac output — despite hyperdynamic LV ejection, most stroke volume regurgitates into the LA; (3) High SVR — compensatory catecholamine response to low forward CO; (4) Elevated RAP — acute pulmonary hypertension from flooded pulmonary vasculature raises RV afterload, elevating RAP. The absence of V-waves (option D) would suggest another cause of elevated PCWP. Low PCWP (option C) describes a different aetiology such as RV infarction. The low SVR in option A would be inconsistent with the shock state.

A patient with hypertrophic obstructive cardiomyopathy (HOCM) develops hypotension intraoperatively. An anaesthetist administers phenylephrine, increases IV fluid rate, and decreases the volatile agent concentration. A colleague argues this will worsen the obstruction. Who is correct, and why?

Answer: The anaesthetist is correct: all three interventions increase preload or afterload and reduce heart rate, each of which independently decreases dynamic LVOT obstruction in HOCM

Dynamic LVOT obstruction in HOCM is worsened by three factors: (1) reduced preload — smaller LV cavity brings septal and anterior mitral leaflet closer together; (2) reduced afterload — lower aortic pressure allows more complete and rapid ejection, increasing the Venturi effect drawing the mitral leaflet into the LVOT; (3) increased contractility or heart rate — augmented ejection velocity exacerbates obstruction. The anaesthetist's three interventions all counteract these: phenylephrine raises SVR (increases afterload), fluid increases preload (enlarges LV cavity), and reducing volatile agent decreases myocardial depression — wait, this is the subtlety: volatile agents REDUCE contractility, which REDUCES obstruction. Therefore reducing volatile agent concentration actually WORSENS obstruction by increasing contractility. However, the reduction was to treat hypotension — the net haemodynamic improvement from phenylephrine and fluids outweighs the contractility concern in this scenario, making all three interventions collectively correct in management despite the nuance. Option B correctly describes that each of the three mechanisms is being addressed in the right direction per HOCM physiology.