Part XX- Episode 3- Unintended Consequences- The Advent of Myocardial Protection Standing on Tall Shoulders- The History of Cardiac Surgery by Thomas N Muziani PA-C, CP

“Two things are infinite: The universe and human stupidity; And I am not sure about the universe”

Albert Einstein- 1955

Author’s note: – It is doubtful that Einstein was ever convinced of an infinite universe. Prior to Edwin Hubble’s published observations in 1929, it appears Einstein held a belief in a static universe. After Hubble’s conclusions providing evidence of an expanding universe, corroborated by Christian Doppler’s- Doppler Shift, Einstein wrote of an expanding universe. tm

Prologue-

Implementing the mechanical complexity necessary to reroute a human’s circulation and supplant functioning lungs with the heart-lung machine created a seismic shift. There have been numerous attempts over the intervening years at eliminating the need for the machine with outcomes open to debate. One very prominent American surgeon when asked his thoughts regarding eliminating the heart-lung machine for certain procedures, reflected-then surmised: “Well…it’s like making love in a hammock standing up. Sure you can do it…but why?”

Denis Melrose and his vision

The most sublime yet challenging final component of rerouting a human’s circulation and oxygenating the blood still remained unanswered; simply stopping then restarting a beating heart. Stopping a beating heart is not difficult, history has validated that. What remained formidable and elusive was how to keep the heart alive, quiet and expecting an uneventful restart into normal sinus rhythm.  The conceptualization of actually providing cardiac protection during this first phase in 1955 was just that; a concept…and a very incomprehensible one at that.

From all historical literature, the prevailing attitude of cardiac surgeons during this early period was the acute desire to simply arrest the heart. Prima facie was a quiet, bloodless field to operate. Even though surgeons were cognizant of the fact this simple act directly conflicted with the physiologic demands of the myocardium…they were all willing to accept that risk.

Denis Melrose was aware of all this. His early experiments resulted in less-than-ideal resumption of normal contraction. However, they were at least resuming electrical activity on a somewhat routine basis. Encouraged by that mere fact, he set out to improve the experiments. He began with utilizing isolated perfused hearts infused with oxygenated Locke’s solution. The hearts Melrose chose for this set of experiments came from five rabbits, a guinea pig, a kitten and a puppy. With myocardial temperatures between 23°C and 37°C he achieved diastolic arrest within 10 to 20 seconds after injecting a syringe with 5mg/ml potassium citrate. Quiescence was maintained as long as potassium citrate remained in the coronary circulation. When reperfused with pure Locke’s solution (which contains K+), Melrose reported a consistent return to normal, spontaneous beating.

With growing confidence that he could achieve arrest and restart, Melrose now began experiments with intact animals. Utilizing 2ml 25% potassium citrate mixed with 20ml whole blood, he injected the mixture into the aortic root of dogs. They were able to achieve rapid arrest with reanimation after 15 minutes of zero coronary flow.

Melrose concluded his Lancet submission stating: “The oxygen consumption of the quiescent heart is very low, and at normal body temperature, cessation of the coronary circulation for over fifteen minutes does not endanger the heart. Although a great deal of further work remains to be done, this method may offer an opportunity for useful surgery on the motionless heart, without the danger of air embolism.”

Approximately two years after this breakthrough publication, several very significant discoveries were published. The first; Melrose and colleagues demonstrated they could extend the “safe” period of arrest to 30 minutes. They also theorized they could achieve even longer durations of arrest by substituting Locke’s solution with oxygenated blood. Second; H.H. Bentall and Melrose conducted a completely separate study and discovered that lactic acid concentrations in the coronary effluent after administering potassium citrate were about one-third as high compared to arrest with zero potassium. It became readily apparent that although the arrested heart was not performing any work…this was still an ischemic organ with a quantifiably significant metabolic uptake.

In 1958, while at Stanford University Hospital, Melrose and Frank Gerbode published their collaborative work with potassium citrate arrest in 34 clinical cases of cardiac surgery. Gerbode’s prescient technique involved 1 part potassium citrate with 9 parts oxygenated blood. In writing about their method of induction, they stated: “The injection is terminated when the heartbeat ceases, no fixed quantity being given, and excess is avoided.”

Authors note: Upon fulfillment of my military obligation I had the privilege of working with a cerebral, visionary surgeon. For cardioplegia we preferred to use Richard Sarns’ “coronary bubble trap” with ¼” Silastic tubing. We injected a syringe of potassium chloride into the bubble trap until the heart entered quiescence. This was directly based on Frank Gerbode’s technique, a true pioneer that is rarely mentioned. Due to such large dynamic holdup of blood in the bubble traps, the heart would not see potassium until quite a bit of blood had been delivered. For cooling we used the Sarns bullet heat- exchanger which is extremely efficient. This was microplegia before the term entered our lexicon.

Fig. 1 Sarns Bubble Trap- entry/egress from bottom- bubbles will float to top. Photo by Jeffrey Sites

In none of the cases did the heart fail to resume normal activity. However, in the discussion section that followed this publication, Melrose made an astute observation when he cautioned: “No patient has yet lived for many years after elective arrest and we must wait on time for judgement as to its real merits.” During these early years, the Melrose technique gained widespread popularity and universal appeal.

Then, during the latter years of 1950’s and early 1960’s, surgeons and investigators began witnessing unintended consequences post-surgery with potassium citrate cardioplegia. They vocalized and wrote about their concerns regarding safety of use. In 1957, Peter Allen and C. Walton Lillehei both cautioned that potassium citrate arrest should be avoided, if possible, in patients with extensive myocardial damage due to any cause. Others reported the frequent occurrence of dysrhythmias after potassium citrate arrest.

When reports of suboptimal outcomes with Melrose solution became too widespread, several investigators returned to the laboratory to dissever the technique and re-evaluate the methodology. In 1959, V.L. Willman and associates published one of the first detailed examinations of myocardial function post recovery from cardioplegia injection. Their studies with dogs discovered that cardiac arrest for 30 minutes with 2.5% potassium citrate resulted in profound, non-retracting decrease in cardiac output, cardiac stroke work and total workload. Also in 1959, James A. Helmsworth and coworkers reported in dog’s the evidence of unusual rigor of the left ventricle, irreversible ventricular fibrillation and focal necrosis after thirty minutes of utilizing Melrose solution.

John A. Waldhausen and Viking Olov Björk, in 1960 and 1961 respectively, confirmed the findings of Willman and Helmsworth. Björk stated: “The potassium method of Melrose seems to be rather dangerous and doubtful one.” Waldhausen and colleagues wrote:

“The majority of patients operated upon for heart disease have increased myocardial workload and although a successful correction of the anatomic lesion may substantially reduce this, the trauma of the operative procedure may offset this beneficial effect in the early postoperative period…Thus, the additional depression of ventricular function caused by cardiac arrest may be sufficient to result in fatal heart failure.”

It became too apparent in reviewing these publications that each investigator was compelled to advocate some alternative method for inducing quiescence. Waldhausen advocated utilizing intermittent aortic occlusion. Viking Björk was convinced hypothermic arrest was preferable. By 1960, primarily due to an extremely comprehensive and well researched report in the Journal of Thoracic and Cardiovascular Surgery conducted by National Heart Institute’s James McFarland and colleagues, there appears to have been universal abandonment of the Melrose technique. McFarland cited two deaths of patients post-surgery that upon autopsy displayed histopathological evidence of severe necrosis. This compelled McFarland and his associates to re-examine the hearts of all patients who died after open-heart procedures at their institution. Their report was rather stunning. Histological examination revealed distinct clinical and pathological evidence of myocardial damage in 79% of their patients subjected to potassium citrate arrest. The lesions were typically viewed as multiple, sharply defined microscopic areas of necrosis emanating within the central portion of the ventricular myocardium.

This graphic evidence compelled the National Heart Institute to issue a voluntary cessation of use for Melrose solution and offer the adoption of intermittent aortic occlusion or direct coronary perfusion.

Over the ensuing fifteen years cardiac surgery reverted to the rather antiquated and pedestrian forms of myocardial protection; direct coronary perfusion with Spencer-Mallet cannulaes if the aorta was opened, intermittent cross clamp with and without an electrical fibrillator, topical hypothermia, usually with ice slush or cold saline and normothermic ischemia. All of these techniques had inherent drawbacks and were less-than-ideal in application. All of these techniques were heavily reliant on minimizing ischemic time. Therefore, the one positive that evolved by this reversion on myocardial protection was the fine-tuning of surgical dexterity and the acute awareness of hypoxic time constraints. Agile surgeons that maintained a mental game plan for each procedure experienced repeated positive outcomes.

As Dr. W. Bigelow once said: “I always thought that patients never got enough credit for having courage”