Joseph and the Amazing Technicolor Dreamcoat The Wonderful Variants of Cardioplegia Composition by Thomas N Muziani March 2023

The current plethora of cardio-protective strategies, combined with the evolution in historical parallel performing a myriad of cardiac operations…are essentially an amalgam to the many years involving trial and error.

As a result, numerous techniques evolved to obtain a reproducible end result limiting the onset of intra-operative tissue ischemia created by the operation, thereby ensuring long-term global protection of the myocardium. The adoption of a particular cardioplegia solution by design over another, more often than not, favored the philosophical dictum of Dr. Ross Ungerleider:

 The August personage of Dr. Ross Ungerleider expressed accurately exactly how most cardioplegia solutions have been chosen over the past fifty years:

“The selection is more a matter of “Immanence based” medicine…rather than “Evidence based”. You used what you trained with. That was the summation of science.

While performing a cursory review over the last fifty years of surgical cardiac protection strategies, it became necessary to assess sequentially all progress that ultimately created the blueprint commonly referred to as “intra-operative myocardial management”. It’s genesis could not be considered “high tech”, it could not even be called “low tech”…if it resembles anything, it would look like “no tech”..

Normothermic ischemia;

Pioneered by Norman Shumway at Stanford University in 1957, “normothermic ischemic arrest” became standard arresting practice for myocardial management prior to the acceptance of intra-cardiac cardioplegia solutions. This is one of the instances that stands out in our Cardiac History due to the fact that two distinct camps emerged and the political rancor was robust. The first group of surgeons maintained “Normothermic ischemic arrest” should be the primary technique when “quieting” the heart. The second group of surgeons believed devoutly that normothermic arrest did not provide enough of a safety valve to guard against the onset of ischemia. They preferred a cold water bath, circulating solution or not, or ice-slush encapsulating the pleural cavity.

There were numerous institutions that embraced Shumway’s technique of topical ice-slush. However, with the advent of electro-chemical arrest utilizing high doses of potassium, topical ice-slush naturally coalesced into the overall procedure of “myocardial protection”. It should be noted that topical ice-slush served well for slowing metabolic uptake of the heart with a cross clamp applied of less-than two hours. Unfortunately, where heart and lungs remained quiescent for two hours plus, the patients lungs periodically would not respond well to prolonged exposure of ice-slush thereby promoting the onset of atelectasis. It must be remembered this was a period in time where it was still very much in vogue to smoke three packs per day of unfiltered cigarettes.

The varied assortment of current myocardial preservation techniques have revolutionized outcomes post cardiac surgery. The menu of varied cardioplegia compounds literally runs the gamut in terms of compounding composition. That the varied techniques appear to accomplish the ultimate goal of global quiescence and reversal of the myocardium is a testimony to the kindness bestowed Cardiac Surgery by some Deity.

Presently, utilized somewhere on this planet, you will discover a cornucopia of varied compounded compositions to achieve electro-chemical arrest of the myocardium. A sample of various formulas/techniques to achieve quiescence remind one of the title to Andrew Lloyd Webber’s musical: “Joseph and the Amazing Technicolor Dreamcoat”. Pick a color-choose a solution…hopefully you will create a Dreamcoat;

Varied Myocardial Preservation Techniques as of 2023

1) Hypothermia (the first viable application directly associated with myocardial preservation)

2) Hypothermia with fibrillator

3) Fibrillator

4) Pure crystalloid solution

5) Crystalloid solution with Pink tinge

6) High K+ or Low K+ delivery

7) Warm vs Cold cardioplegia

8) Warm plus Cold, intermittent and continuous, with substrate enhancement

9) Continuous vs Intermittent perfusion

10) Flowing through vein grafts

11) Antegrade and/or Retrograde delivery

12) Pure whole blood (cold and warm) with micro-titrations of drugs (microplegia)’

13) del Nido single dose low K+ with Lidocaine and Magnesium

14) Bretschnider single cross clamp

This panoply of cardio-protective strategies utilized during intra-operative cardiac surgery has surprisingly established a somewhat adversarial stance regarding fidelity to one’s choice of solutions. Alignment towards one side or the other of this imaginary dividing line theoretically deprives the patient from the benefits of each solution if they are discarded due to perception of fidelity or loyalty to one technique over another.

Cardio-protective strategies, in the same way as cardiac operations have been refined to the point that it is mandatory to comprehend and, if need be, utilize various techniques in order to achieve absolute reduction of intra-operative damage in concert with a technically perfect operation assuring a positive outcome.

The 1960’s and 70’s provided a Golden Moment for cardiac surgery and myocardial protection. Published literature on cell energetics along with the content and function of ATP were first chronicled. In 1974 Mitchell characterized mitochondrial respiration along with the ATP producing proton circuit. Mitchell also eloquently described the diverse role of ATP as the life-giving molecule along with the mechanism of its transport to gain functional recovery

With cardioplegia and ischemic research two energy related concepts became subject to considerable debate: time and temperature limits for expected survival from surgical ischemia; and mechanisms plus causation of ischemia-induced contracture.

“Buying” Resuscitation Time;

Bretschneider’s belief was to accept an uninterrupted extended period of total ischemia which he maintained should be well tolerated with the application of cold chemical cardioplegia. His primary attention focused on conservation of cell energy. His proposal was that chemical arrest spared cell ATP stores, maximizing the use of hypothermia which delayed ATP depletion. Coupling this strategy, compounding an appropriate buffering system should induce the anaerobic production of a minor, but extremely important amount of ATP. He then presented the concept of practical resuscitation time or t-ATP. This is the time required for myocardial ATP to drop from 6 mmol/g wet weight to approximately 4 mmol/g wet weight. Bretschneider firmly believed that ATP at this level was critical to obtain functional recovery from ischemia thereby allowing the ability to rapidly wean from CPB.

The “Stone Heart” dilemma;

Through the years of 1967 and 1969 became a clarion call for reevaluation and rethinking myocardial preservation techniques. During this period, reports first appeared (Taber et al. 1967; Najafi et al. 1969) documenting transmural,  or subendocardial myocardial necrosis (Cooley et al. 1972) and low cardiac output post valve replacement. In 1972, Cooley, an extremely vocal proponent of normothermic ischemic arrest (Cooley et al. 1962), described “stone heart” (Cooley et. al. 1972).

“Stone heart” became the term applied to irreversible contracture of the myocardium that would occasionally occur following non-protected aorta.