Part XXVI- Episode 9- Chronic Heart Failure And Myocardial Energetics – Standing on Tall Shoulders – The History of Cardiac Surgery Thomas N Muziani PA-C, CP

“The best physician…is also a philosopher” Claudius Galenus- “Galen”- (200 BC – 129BC)

The Failing Heart:

Chronic heart failure in 2019 has unfortunately evolved into an extensive medical and therefore societal dilemma. It is now classified as a common disease affecting more than 2% of the populous in the United States, some five million people. Even more alarming, approximately 30 to 40% of these patients will die from heart failure within 1-year post diagnosis. The most sobering aspect of this disease; confronting the reality imposed from the financial burden of heart failure due to our aging population compounded with the plethora of new modalities utilized to treat “perceived” root causes.

Chronic heart failure today remains a significant factor in perioperative mortality and morbidity during cardiac surgery within a large number of patients. The genesis for this condition appears to be attributed to impaired preoperative cardiac function. Even minimal or transient cardiac injury while in operating room resulting from poor or inadequate global myocardial protection may significantly influence patient outcomes.

In order to fully convey the nuances that determine heart failure it will be necessary to revisit the intricacies of myocardial energetics. It is universally agreed upon that key aspects of the cardiac energetic system become down regulated in the failing heart. Under conditions that would be considered normoxic, mitochondrial oxidative phosphorylation generates approximately 95% of the ATP content in a human heart. This is absolutely necessary to trigger the process of excitation contraction, along with maintenance of membrane transport systems. Voluminous studies on patients with end-stage cardiomyopathy have validated the total adenine nucleotide pool (ATP, ADP, and AMP), creatine kinase activity, which is required for ATP synthesis. These factors are all markedly decreased in the failing heart.

Although multiple mechanisms have been postulated to rationalize the grossly abnormal energetics that occur in the failing heart, recent validation in our understanding of mitochondrial cell biology has proffered a wonderful possibility. Mitochondria targeted therapeutics as a target specific drug may provide the long-sought increase in energy production.

As was mentioned in a previous article, patients presenting to operating room with severe left ventricular dysfunction or cardiogenic shock will not tolerate aortic clamping or extended periods of ischemia. This has been isolated to pre-ischemic depletion of myocardial energy stores. When adhering to the myocardial protection philosophy of warm induction, cold maintenance and warm reanimation, the expected result should be recovery of myocardial energy stores. Resuscitating these energy stores will provide improved overall hemodynamics along with strengthened ventricular function allowing for an accelerated, uneventful recovery.

Patients Presenting in Cardiac Arrest:

A dynamic that is seldom discussed is the patient presenting to operating room in cardiac arrest. Unfortunately, too much reliance is placed on the ability of Anesthesia to provide some magical panacea between when the patient is placed on the operating table and going on bypass. The reality becomes evident that Anesthesia is restricted by having only two avenues to provide stabilization during this “golden” period; volume and/or drugs. Military medical experience has corroborated that both modalities are not the treatment of choice and may prove counterproductive.

If the heart-lung machine is set up and primed, it will become the surgeon’s and patients’ best friend. Going on bypass ASAP, even partial femoral or suction bypass WARM will immediately produce remarkable results. Partial bypass at 2-3 liters per minute warm can reinvigorate the myocardial energy stores with more expediency and thoroughness than any other mechanism. Extreme caution should be exercised to not overuse vasopressors or inotropes. They will clamp down the vascular bed, including coronaries, which serves no practical positive purpose. Flow is the patients’ best friend along with warmth.

One last empirical anecdote; it is futile and counterproductive to expect a positive resolution when defibrillating a cold heart. When a human heart detects 33⁰C or below, it wants to fibrillate and applying the paddles to cardiovert is diverting precious time and energy when either one is not readily available. Warmth and flow are key primary focus.

Membrane Polarity and Reduced Inflammation:

The etiology of postoperative cardiac surgery complications for both adults and pediatric congenital corrective operations is multifactorial. It will include age, gender, ethnicity, cardiopulmonary bypass times, technical difficulty and urgency of operation. Other pertinent factors are; temperature transitions, low preoperative left ventricular ejection fraction along with pre-existing medical conditions.

These conditions may include: diabetes, obesity, renal disease, smoking, hypertension, along with metabolic disorders. Then, as if this dyscrasia soup isn’t complicated enough, include high potassium concentrations formulated in cardioplegia solutions. There is a direct correlation between high metabolic potassium levels and postoperative cardiac dysfunction with related morbidity.

Since cardiac repair still requires a quiescent heart, it is necessary to impose a physiologically unnatural transitional process commencing with a warm extracellular, normokalemic, aerobic environment in which the membrane potential of cardiac cells exist in a polarized state. Then we intentionally impose a hostile climate of cold ischemia where the cardiac cells become depolarized…just to reverse the order and return to a normal warm polarized state. It is easy to understand the potential for triggering myocardial and endothelium injury. Currently 99% of present-day cardioplegia solutions and almost all organ preservation solutions include high potassium concentrations to depolarize the myocardial cell membrane potential from its natural polarizing voltage of -80mV augmenting to approximately -50mV. Potassium does not possess the inherent properties to completely shut down cardiac membrane-ion pumps during the process of “quiescence”. The illustrative analogy that conveys a comparison is the step-down transformer and cord that charges your cell phone. If you observe your cell phone charger, you will notice a little box attached to the power cord. This is a step-down transformer, reducing the voltage coming from your electrical outlet to the appropriate charging voltage to replenish your phone batteries.

When you remove your cell phone from its charging cord, most of us have the mis-impression the cord alone is no longer capable of drawing any electrical current. That would be incorrect. As long as it is plugged in, it will always draw some current. We suffer the same mis-impression regarding potassium’s inability to completely shut down all electrical activity in the myocardium. There are still membrane-ion pumps that remain active and are constantly drawing some current. This slow electrical depletion on the myocardium will trigger the ischemic cascade providing a false sense of adequate myocardial protection…especially during long duration, single-clamp, one dose scenarios. Apply a tourniquet for one hour to your upper arm and you will graphically witness the effects of ischemia.

The cardiac membrane of the atria, Purkinje fibers, and ventricles behave as a potassium electrode. During diastole, the membrane potential approaches a Nernstian* potassium potential over a complete spectrum of extracellular potassium concentrations. Once extracellular potassium concentrations exceed 16mmol/L (-50mV), the sodium fast channel availability and sodium conductance are dramatically reduced thereby causing the heart to arrest during the diastolic phase. The electro-mechanical process created by potassium-induced depolarized arrest has a direct link with ionic and metabolic imbalances, where Na⁺ and Ca²⁺ loading may lead to myocardial dysfunction and microvascular injury.

High potassium concentrations are an extremely powerful coronary vasoconstrictor and pro-spasmodic agonist, which may lead to increased vascular resistance impairing delivery of intra-myocardial cardioplegic solutions. Myocardial hypothermia may attenuate some constrictive effects. However, usually coronary dysfunction along with spasm may still occur.

The influence of polarizing cardioplegia solutions on membrane polarity have been shown to play a role in reducing the inflammatory response and associated coagulation disorders triggered by surgical trauma along with the impact of cardiopulmonary bypass. Ward and colleagues in 2006 published that emigrated neutrophils after adhering to ventricular myocytes, prompted an immediate membrane depolarization, contributing to an inflammatory-linked generation of arrhythmias, cell injury along with contractile dysfunction.

Ward et. al further validated holding the membrane potential in a natural “resting” non-depolarized state would reduce cell damage as a result from inflammatory attack. Their collective conclusion: “Thus maneuvers that precluded activation of sodium channels, for example, holding the resting membrane potential at -80mV, significantly increased time to cell death or prevented contracture entirely”.

Hans Bretschneider’s pioneering work in 1964 on creating a viable cardioplegia capable of uninterrupted long periods of total ischemia concentrated on conservation of cell energy. Therefore, Dr. Bretschneider is now generally considered the pioneer of “one-shot no replenishment” cardioplegia dogma.

However, one fact must never be invalidated; in the intervening fifty-five years, universally, the adult patient population has transformed radically. Clustered co-morbidities, prior interventions both non-surgical and surgical plus an increased aging population are now the standard patient profile. This pertinent issue, coupled with the reality that we still cannot determine a time point when exactly the ischemic cascade will commence, dictates that a “single-dose” of cardioplegia unfortunately provides zero wiggle room ensuring appropriate and complete global myocardial protection.

Constant review and discussion of patient outcomes have always been the most pragmatic and wisest indice of what works and what does not. Time, mortality, morbidity and surgical preference will inevitably dictate which cardioplegia modality becomes the arresting agent de jour.

Applying the concepts of biomimicry, imitating the elements of nature to solve complex human problems, should be the logical approach to the next generation of myocardial protection. The common example provided to illustrate how biomimicry works is Velcro. In the 1940’s, a Swiss engineer, George de Mestral, was hunting in the Jura Mountains with his dog. He noticed that cockleburs would stick to his pants, socks and his dogs’ fur and held on tenaciously when attempting to pull them off. The concept of Velcro was born and became a perfect example of observing nature to procure a practical solution. With that in mind, it would be wise to remember that no other animal on this planet utilizes potassium to regulate their furnace.

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Perfusion Theory is an educational platform for the Oxygen Pressure Field Theory (OPFT). August Krogh’s theoretical concept of the oxygen pressure field is explained and then applied to clinical applications in perfusion practice.