Myocardial Protection

Question 1

What is the relationship between troponin and CK-MB levels post-cardiac surgery and 30 day and long term mortality?

Answer 1

There is a relationship between increased troponin or CK-MB levels post-operative day 1-2 and mortality post-cardiac surgery

Question 2

What are the primary mediators of ischemia/reperfusion injury?

Answer 2

ischemia induced intracellular calcium overload and oxidative stress induced by ROS at the onset of reperfusion

Question 3

How does reperfusion injury cause myocardial stunning or death?

Answer 3

Reperfusion -> Reactive oxygen species -> damage to sarcoplasmic reticulum calcium channels and contractile proteins -> myocardial stunning

Reperfusion -> Reactive oxygen species -> calcium overload -> collapse of mitochondria membrane potential and cell death

Question 4

What are the three major types of cardioplegic solutions and name one example from each

Answer 4

Intracellular crystalloid cardioplegia - Bretschneider’s or Roe’s
Extracelllular cyrstalloid cardioplegia - Del Nido’s or St Thomas
Blood cardioplegia - Cold vs Warm

Question 5

What is the most common form of cardioplegia used in the US and why?

Answer 5

Cold blood cardioplegia because it provides an oxygenated environment and provides a good buffering capacity, osmotic properties, is physiologic and limits hemodilution

Question 6

What is miniplegia?

Answer 6

Undiluted blood cardioplegia

Question 7

What are the differences between cold blood vs cold crystalloid cardioplegia?

Answer 7

The evidence shows either is safe and effective, cold blood may cause a lower incidence of low cardiac output syndrome and less CK-MB release

Question 8

What are the differences between Cold vs Tepid vs Warm cardioplegia?

Answer 8

The evidence suggests warm may be associated with lower mortality but higher neurologic events. A “hot shot” before cross clamp removal may accelerate myocardial recovery. Tepid cardioplegia may be associated with reduced lactate release. Overall though, all three methods are similar, there is not one that is superior.

Question 9

What are the differences between antegrade vs retrograde cardioplegia?

Answer 9

Antegrade cardioplegia is delivered into the root, it can be inadequate in severe CAD and moderate or severe AI. Retrograde cardioplegia is delivered into the coronary sinus, it can delivered inadequate protection to the RV and be inadequate in PLSVC. No method is superior, but using both provides the best protection especially in cases of poor LV function, AI, severe CAD/LM and anticipated long clamp times.

Question 10

What is better, intermittent or continuous cardioplegia?

Answer 10

One study suggested better hemodynamics and lower use of inotropic agents with continuous cardioplegia but there were no differences in patient outcomes and troponin/CK levels post-operatively. Neither method is superior to the other but more research needs to be done. However, intermittent cardioplegia is better for a dry quiescent operative field.

Question 11

What is intermittent aortic cross-clamping?

Answer 11

During on-pump CABG, it usually involves cooling the patient to 30-32C and intermittently removing the cross clamp at the completion of each graft and allowing the heart to fibrillate at other times. It is considered safe and a technique for patients with cold agglutinin disease.

Question 12

What is systemic hypothermia and elective fibrillatory arrest?

Answer 12

It is a form of non-cardioplegic cardiac surgery where systemic hypothermia and a high systemic perfusion pressure of 80-100 allows for CABG or mitral valve surgery. Proximals are performed during short periods of hypothermic circulatory arrest and distals are performed locally occluding the coronary artery with vascular clamps or sutures.

Question 13

What is ischemic preconditioning and what is the clinical relevance?

Answer 13

It is an endogenous adaptive phenomenon whereby the heart becomes more tolerant to a period of prolonged ischemia if first exposed to brief episodes of coronary artery occlusion. Researchers have noted that patients experiencing angina prior to MI have a better in hospital prognosis and long term survival than those who did not.

Question 14

What are the molecular channels implicated in ischemic preconditioning?

Answer 14

The inhibition of mPTP (mitochondrial permeability transition pore) and mK(atp) channels. mK(atp) channels reduce calcium overload, mitochondrial ROS production, swelling and preserve ATP levels after ischemia/reperfusion

Question 15

Which medications can cause ischemic preconditioning?

Answer 15

Adenosine, nitroglycerin, bradykinin, nicorandil

Question 16

Which medications block ischemic preconditioning?

Answer 16

Naloxone, aminophylline (adenosine antagonist), glibenclamide (Katp channel blocker)

Question 17

What is ischemic postconditioning?

Answer 17

The concept introduced by Zhao in 2003 refers to rapid intermittent interruptions of blood flow in the early phase of reperfusion which demonstrated reduced infarct size in preclinical studies and reduced biomarker release in clinical studies

Question 18

What is remote ischemic preconditioning?

Answer 18

The concept that ischemic preconditioning done in a different area or even different organ can result in the same beneficial effects of ischemic preconditioning. i.e. IPC of the circumflex can reduce infarct size in an LAD infarct.

Question 19

What is the evidence surrounding remote ischemic preconditioning?

Answer 19

While there was some initial excitement about the potential reduction in troponin release with Thielmann’s RCT in 2013, the trials RIPostCond, RIPHeart Study and ERRICA trial were negative and as a result RIPC is not a therapeutic modality in cardiac surgery at this time.

Question 20

What is autophagy?

Answer 20

Autophagy is an endogenous protective response whereby a autophagosome sequesters cytoplasmic components and recycles them by fusing with a lysosome. Upregulated autophagy protects against cell death induced by ischemia reperfusion and CPB and heart surgery downregulates autophagy.

Question 21

What is the effect of adenosine in cardiac surgery?

Answer 21

The effect is unclear, with some studies showing benefit in terms of reduced cardiac enzymes, reduced LOCS, reduced pressor use post cardiac surgery, but this is not consistent across all studies.

Question 22

What are NHE-1 inhibitors?

Answer 22

NHE-1 inhibitors are sodium-hydrogen exchanger inhibitors that block NHE-1, which contributes to cell death in ischemia. In the EXPEDITION trial, the NHE-1 blocker cariporide did reduce the incidence of post-op MI by 18% but mortality was higher at 2.2% vs 1.5% in placebo which was mostly attributed to an increased number of cerebrovascular events. As a result, NHE-1 inhibitors are not used in practice.

Question 23

What is Glucose-Insulin-Potassium aka GIK?

Answer 23

GIK is a solution that has been shown in some studies to reduce peri-op MI, post-ischemic myocardial dysfunction and a-fib post-cardiac surgery, but the evidence is still mixed. A definitive trial needs to be conducted to form a more concrete conclusion.

Question 24

How is cyclosporine purported to provide myocardial protection?

Answer 24

Cyclosporine is purported to provide myocardial protection by inhibiting the opening of mPTP (which would lead to cell death). Early studies showed some promise but the Circus trial in STEMI patients showed no difference in a composite outcome (death, worsening heart failure during initial hospitalization, re-hospitalization for CHF or adverse LV remodeling) at 1 year.

Question 25

What is the pressure of antegrade cardioplegia? How about ostial cardioplegia?

Answer 25

200mmHg for antegrade, 150 for ostial

Question 26

What is the flow rate of retrograde cardioplegia? What is the pressure?

Answer 26

200-400mL/min is the flow rate and pressure is 30-50mmHg