Version classiqueVersion mobile

Animals and Medicine

 | 
Jack Howard Botting

II. Development of Life-saving Procedures

10. Cardiopulmonary Bypass: Making Surgery on the Heart Possible

Note de l’auteur

An earlier version of this chapter was published as: Cardiopulmonary bypass – making surgery on the heart possible. RDS News July 1995 8-12.

Texte intégral

1In the early seventeenth century William Harvey established that there is continuity between arteries and veins, and that the heart pumps blood through these vessels in a circular fashion. Harvey developed his hypothesis by observation of the relatively slowly beating hearts of cold blooded animals, such as snakes, rather than those of warm-blooded animals, which beat too fast to detect the pattern of their motion. In his use of further observational and quantitative techniques to substantiate his theory, Harvey manifested an exceptional intellect and imagination.

2Even Harvey, however, could not have imagined the progress in the treatment of cardiovascular problems that was to occur in the following threeand-a-half centuries. Today, a patient’s heart and lungs can be temporarily supplanted by a mechanical pump and oxygenator. The heart can be stopped for many hours, opened and subjected to intricate surgery, such as the replacement of a heart valve with a manufactured prosthesis or with animal tissue. At the end of the operation the repaired heart and the lungs are re-plumbed into the circulation where they resume their normal function.

3This technique of open heart surgery involves opening the chest and the catheterisation of the great veins carrying the blood returning to the heart from the system. This deoxygenated, venous blood is collected in a reservoir, then passed through an oxygenator. The freshly oxygenated blood is pumped back into the arterial circulation through a convenient artery. Thus, an adequate supply of oxygenated blood is maintained to the vital organs. The heart and the lungs are therefore out of the circulation, having been “bypassed” by the mechanical pump, functioning as the heart, and the oxygenator, standing in for the lungs.

4The heart is rendered quiescent and kept viable by cooling and by perfusion of the coronary arteries with a “cardioplegic” solution, which prevents the heart beating and also supplies the heart with requisite nutrients and electrolytes. The artificial heart-lung circuit is filled with blood of the same group or with a synthetic priming solution, and clotting is prevented within this extracorporeal circuit by the use of heparin. The sudden increase in apparent blood volume when the patient is connected to the extracorporeal circulation requires appropriate adjustment of anaesthetic level. Under these conditions the heart can be operated on for many hours. Even long and delicate procedures such as the replacement of a heart valve can be performed at a leisurely pace.

5It is hardly imaginable that anyone could believe that a procedure of this complexity, with many potential difficulties, such as the development of lethal air or clot embolism, could have been achieved without many pilot experiments in relatively large mammals (Table 1). However, animal rights literature asserts that it is a “fiction” to say that open heart surgery depended on animal experiments (1).

ANIMAL EXPERIMENTS AND OPEN HEART SURGERY

1916-35

Discovery and purification of heparin

Dog, pig, ox

Development of extracorporeal technique

1933-53

Cat, dog

Pumps and oxygenators

1955-85

Elective cardiac arrest and preservation of the ischaemic myocardium

Dog, rabbit, rats

Early Experiments

6The first use of cardiopulmonary bypass in a patient was by Gibbon in 1953. However, Gibbon had started experimental work on the technique 19 years previously. As is frequently the case, a particular clinical experience prompted Gibbon to consider this possible surgical innovation. In 1930 one of his patients died because of obstruction of the pulmonary artery with a massive embolus. This naturally provoked the thought that the blockage could have been successfully removed, and her life preserved, if even a portion of the patient’s circulation could have been taken over by an extracorporeal heart and lungs (2), thus bypassing the obstruction in the pulmonary artery.

7It was 4 years before Gibbon and his wife had the opportunity to test this technique in the Surgical Research Laboratories of the Massachusetts General Hospital. They found, to their surprise and delight, that it was possible to take over part of the pulmonary circulation of the cat by an artificial, extracorporeal circuit for four hours, with the cardiorespiratory function being adequately maintained (3). Repetition of the experiments under sterile conditions demonstrated that substitution of the heart and lungs of a cat for 20 minutes by mechanical devices was followed by recovery and survival for more than 250 days in 3 out of 13 animals. The remainder survived for between 1-23 days. In control experiments, simple occlusion of the pulmonary artery for 3½ minutes, with no bypass, produced permanent cerebral damage. Death always followed a 6½ minute occlusion (4).

8During these early experiments on cats, Gibbon tested various types of pump and oxygenator. It was established that a pulsatile flow (such as occurs with the heart) was not essential for the proper functioning of the perfused organs. This meant that a comparatively simple roller pump could be used as a mechanical heart (perhaps surprisingly, roller pumps were found not to cause excessive breakdown of red blood cells). The oxygenator originally used by Gibbon was a rapidly moving hollow cylinder constantly gassed with a 95% oxygen, 5% carbon dioxide mixture. The withdrawn venous blood was trickled against the inner surface of the cylinder where it was spread into a thin film by centrifugal force. Oxygenated blood was collected at the bottom of the cylinder from which it was pumped back into the animal. Gibbon opted for this method of oxygenation since, unlike other techniques, it did not cause undesirable frothing.

9Gibbon also established that, contrary to belief, large arteries (such as the femoral) could be catheterised and ligated, for the return of the blood to the circulation, without compromising the tissue normally served by the artery (2).

Refining the Technique

10There was a hiatus in research from 1939-1945. Gibbon and others then began extensive experiments in dogs to perfect a technique whereby complicated and time-consuming operations could be performed inside the chambers of the heart, without the problems associated with complete occlusion of the vessels carrying blood back to the heart.

11In a comprehensive paper, Gibbon described a series of experiments in dogs to test whether exclusion of the heart and lungs from the circulation and prolonged passage of the blood through an artificial lung would have any deleterious effect (5). Initial experiments merely involved passing venous blood through the pump and cylinder oxygenator for 80-180 minutes, with no occlusion of the vena cava. This experiment was simply to see if the passage of the blood through the extracorporeal circulation for a prolonged period produced any ill effects. These animals lived less than 12 hours, dying in coma. Post mortem examination showed that death was caused by multiple small clots throughout all the organs. Further experiments demonstrated that the lungs could filter out these microemboli under some conditions, but attempts to pass the blood through the lungs prior to its return to the entire system proved abortive.

12Gibbon therefore included a metal filter into the extracorporeal circuit (300 x 300 micron mesh, thread thickness 140 micron). The apparatus including the filter was then used in 6 dogs for 21/2 hour periods. All 6 dogs recovered rapidly after the operation and no haemolysis was induced by the filter. The animals were sacrificed between 42 and 106 days after the operation.

13No sign of any infarction or damage was seen at autopsy. One of the dogs was observed to have but one kidney, yet even this animal had recovered with no renal complication.

14Armed with the experience of these pilot experiments, Gibbon and his co-workers embarked on full scale heart and lung bypass experiments with the whole of the blood returning to the heart being passed through the extracorporeal apparatus for up to 113 minutes. In initial experiments the mortality in the dogs was 60%, death being due to haemorrhage or anoxia. More sparing use of the anticoagulant, heparin, and the administration of carefully chosen amounts of its antagonist protamine at the conclusion of the bypass reduced the haemorrhage. The apparatus was modified to enable the withdrawal of greater amounts of blood from the vena cava. Oxygen saturation of the blood was improved by placement of wire mesh over the surface of the rotating drum, this prevented filming and promoted greater exposure of the blood to oxygen. These modifications resulted in complete recovery of most animals. A few deaths occurred due to pericardial effusion.

15The next step was to actually open the heart during bypass. Gibbon and co-workers carried out experiments on 29 dogs in which the septum between the atria was pierced under direct vision through the opened auricle. In 24 of these dogs the septal defect was then closed. Fourteen of these dogs survived and the defect became completely healed and covered in endothelium on both sides (6).

16Air entering the heart and hence the coronary circulation whilst the heart was opened was a frequent cause of death during these experiments. However, in 12 experiments a small plastic cannula was placed in the left ventricle via a stab wound. Suction was continuously applied to this cannula, thus any air entering the ventricle was removed. Air embolism of the coronary arteries did not occur in any of these experiments (6).

The First Use of Cardiopulmonary Bypass in Patients

17Thus, twenty years of experimentation enabled the considerable problems associated with the development of an artificial heart and lung machine to be exposed and progressively solved. By the early 1950s the mortality in experimental animals was down to 12%.

18Gibbon was ready to perform the first open heart operations on patients, aided by the heart-lung machine, in 1952-53. The first was on a 15-month-old baby with severe congestive heart failure (7). The cause of the condition was thought by the referral physicians to be a hole in the interatrial septum. When the atrium was opened however, no septal defect was found. The baby died soon after the operation and the post mortem revealed a huge patent ductus arteriosus. Sadly, this defect could easily have been corrected had it been looked for during the operation (Fig. 10.1).

Fig. 10.1 The recently transplanted heart of a baby boy, showing the tubing still connecting it to the heart-lung machine. The donor heart was preserved by injecting it with chilled cardioplegic solution. © Science Photo Library, all rights reserved.

19The second operation was performed on 6 May 1953. The patient was an 18-year-old girl who, although symptomless until December, 1952, had at that time developed right heart failure. Cardiac catheterisation revealed an atrial septal defect.

20The patient was connected to the heart-lung circuit for 45 minutes during which time the heart was opened and the septal defect closed with a silk suture (7). The patient made a complete recovery and was alive and well at least 5 years later (2; Fig. 10.2).

Fig. 10.2 In open heart surgery the heart-lung machine takes over the function of the heart with a pump and the function of the lungs with an oxygenator. This means that surgery, often taking several hours, can be carried out in relative safety to replace diseased arteries or defective valves. © Science Photo Library, all rights reserved.

Elective Cardiac Arrest

21During the early open heart operations the flow of blood to the heart muscle continued through the coronary vessels. The persistent leakage of blood into the heart chambers from the coronary circulation necessitated the constant removal of this blood by suction, in order to maintain a clear field. The heart continued to beat, providing another hindrance to the cardiac surgeon.

22In order to enable the operator to achieve the goal of “the unhurried correction of cardiac abnormalities under direct vision” (8), experiments were made to see if it was possible to stop and restart the heart at will, at the same time ensuring that no damage occurred to the heart muscle.

23Melrose and his colleagues (8) achieved “elective cardiac arrest” in anaesthetised dogs on a heart-lung machine. Potassium citrate solution infused into the heart caused arrest within 5 seconds. After a token operation, blood was allowed back into the coronary vessels. Upon reperfusion with blood the hearts frequently went into ventricular fibrillation. Restoration of normal rhythm with a defibrillator was only possible in 70% of the experiments.

24These researchers therefore performed further experiments on isolated, perfused hearts of rabbits to determine the optimal concentration of potassium necessary to stop the heart, and the allowable duration of the period of arrest. They concluded that potassium ions could be used to stop the heart pumping during bypass operations, and that hearts could recover spontaneously after 15 minutes arrest without becoming damaged. They also demonstrated that administration of calcium salts or adrenaline to restore heart beat was not only unnecessary but dangerous (adrenaline had frequently been used in the clinical setting to restart an arrested heart).

The Development of Cardioplegic Solutions

25During the following decade the problems associated with ischaemia produced in the arrested heart were investigated and gradually solved. This was achieved almost entirely by studies on the rat heart.

26One of the most important factors in the prevention of damage to the ischaemic heart is to stop the heart as rapidly as possible. High magnesium, zero calcium, acetylcholine, neostigmine and tetrodotoxin were all investigated for their ability to produce rapid cardiac arrest (9). Raised potassium concentration was found to be the method of choice, although preservation of the heart was found to be better with the chloride salt, rather than the citrate used by Melrose and his colleagues. Citrate had some toxic effect possibly due to chelation of calcium.

27In a series of painstaking, carefully controlled studies lasting several years, Hearse and his colleagues at St Thomas’s Hospital developed a cardioplegic solution that enabled hearts to be safely subjected to ischaemic periods of 4-5 hours. Their technique was simple. Rat hearts from freshly killed animals were perfused in an in vitro circuit. The hearts were subject to a 30 minute period of ischaemic arrest at 37°C. The post-ischaemic recovery of function (expressed as a percentage of the pre-ischaemic activity) was only 3%, indicating severe and irreversible myocardial injury. However, prior perfusion of the coronary vessels with a solution of potassium chloride (to stop the heart) caused a 10-fold improvement in recovery (i. e. to 30% of control).

28Continuing with this technique, Hearse and his colleagues altered the concentration of various ions and other compounds within the cardioplegic solution (Fig. 10. 3).

Fig. 10.3 Effect of additives on recovery of rat heart from ischemia. Data from D. Hearse (1988), The protection of the ischaemic myocardium: surgical success v clinical failure?, Progress in Cardiovascular Diseases, 30, 6, 381. The graph shows the beneficial effects of sequential addition of protective agents to cardioplegic solution. The protective solution was infused before a 30-min period of ischaemia of the isolated perfused rat heart. Without cardiac arrest the hearts only recovered 3% of their pre-ischaemic activity. With the progressive addition of various ions and chemicals recovery reached over 90%. Concentrations (mmol/L): potassium (K, 16); magnesium (Mg, 16); adenosine triphosphate (ATP, 10); creatine phosphate (CP, 10); procaine (7.4).

29Surprisingly, it became clear that myocardial protection during ischaemia was not merely a matter of potassium arrest, for major differences in protection existed between solutions only slightly different in formulation. Ultimately the cardiac function, following even prolonged periods of ischaemic arrest, was restored to more than 90% of pre-ischaemic levels by the infusion of cardioplegic solutions of optimal composition prior to the ischaemia. Reducing the temperature of the solution to below 28° C (“cold cardioplegia”) produced even greater improvement (10; Fig. 10.4).

Fig. 10.4 Hypothermia and ischaemic injury. Data from Hearse (1988). The graph shows the beneficial effects of hypothermia on the ischaemic heart. Rat hearts were subjected to 60 minutes of ischaemia at various temperatures. Their recovery was measured 15 minutes after the end of the ischaemic period and expressed as a percentage of the activity before ischaemia. Hypothermia produced good protection if the temperature was kept below 24° C.

30Further experiments, usually upon isolated, perfused rat hearts, have investigated the increase in efficacy produced by the inclusion of other chemicals in the standard cardioplegic solutions. Creatine phosphate, adenosine triphosphate, glucose, glutamate, aspartate, calcium antagonist drugs, procaine, glucocorticoids and many other substances have been shown to produce some degree of enhanced protection of the ischaemic myocardium in experimental studies.

31Cold cardioplegia is routinely used in cardiopulmonary bypass operations throughout the world. Over 30,000 such procedures are carried out in the UK each year, with under 5% mortality. The “St Thomas’Hospital No. 1 solution” is almost exclusively used in the UK and widely used in Europe. In the USA St Thomas’solution No. 2 (Plegisol) is approved by the FDA (11; Table 2).

ST THOMAS’HOSPITAL CARDIOPLEGIC SOLUTIONS.
From Ledingham, Braimbridge & Hearse 1987
J Thorac Cardiovasc Surg 93 240.

Composition (mmol/L)

Solution No 1

Solution No 2

Sodium chloride

144

110

Potassium chloride

20

16

Magnesium chloride

16

16

Calcium chloride

2.4

1.2

Sodium bicarbonate

--

10

Procaine hydrochloride

1

--

32Cardioplegic solutions have also been used to preserve hearts prior to transplantation. With such a technique hearts have been successfully preserved for periods in excess of 15 hours (10).

33The normal crystalloid cardioplegic solutions in present use, when cooled, provide good intraoperative protection for most patients. Clinical evaluation of solutions with various concentrations of the additives mentioned above will ultimately provide the best cardioplegic solution even for the high risk patient.

Bibliographie

References

1) British Anti-vivisection Association (London) (1995) Pamphlet: Lies, damned lies... and vivisection.

2) Gibbon J H (1959) Extracorporeal maintenance of cardiorespiratory functions. Harvey Lectures 53 186.

3) Gibbon J H (1937) Artificial maintenance of the circulation during experimental occlusion of the pulmonary artery. Arch Surg 34 1105.

4) Gibbon J H (1939) The maintenance of life during the experimental occlusion of the pulmonary artery followed by survival. Surg Gyn Obst 69 602.

5) Stokes T L & Gibbon J H (1950) Experimental maintenance of life by a mechanical heart and lung during occlusion of the venae cavae followed by survival. Surg Gyn Obst 91 138.

6) Miller B J, Gibbon J H, Greco V F, Smith B A, Cohn C and Allbritten F F (1953) The production and repair of interatrial septal defects under direct vision with the assistance of an extracorporeal pump-oxygenator circuit. J Thor Surg 26 598.

7) Gibbon J H (1954) Application of a mechanical heart and lung apparatus to cardiac surgery. Minnesota Med 37 171.

8) Melrose D G, Dreyer B, Bentall H and Baker J B E (1955) Elective cardiac arrest. The Lancet ii 21.

9) Hearse D (1980) Cardioplegia: the protection of the myocardium during open heart surgery: a review. J Physiol Paris 76 751.

10) Hearse D (1988) The protection of the ischaemic myocardium: surgical success v clinical failure? Prog Cardiovasc Dis 30 381.

11) Ledingham S (1992) Intraoperative myocardial protection, in P H Kay ed., Techniques in Extracorporeal Circulation 3rd ed. Oxford and Boston: Butterworth-Heinemann.

Table des illustrations

Légende Fig. 10.1 The recently transplanted heart of a baby boy, showing the tubing still connecting it to the heart-lung machine. The donor heart was preserved by injecting it with chilled cardioplegic solution. © Science Photo Library, all rights reserved.
URL http://books.openedition.org/obp/docannexe/image/1982/img-1.jpg
Fichier image/jpeg, 64k
Légende Fig. 10.2 In open heart surgery the heart-lung machine takes over the function of the heart with a pump and the function of the lungs with an oxygenator. This means that surgery, often taking several hours, can be carried out in relative safety to replace diseased arteries or defective valves. © Science Photo Library, all rights reserved.
URL http://books.openedition.org/obp/docannexe/image/1982/img-2.jpg
Fichier image/jpeg, 164k
Légende Fig. 10.3 Effect of additives on recovery of rat heart from ischemia. Data from D. Hearse (1988), ′The protection of the ischaemic myocardium: surgical success v clinical failure?′, Progress in Cardiovascular Diseases, 30, 6, 381. The graph shows the beneficial effects of sequential addition of protective agents to cardioplegic solution. The protective solution was infused before a 30-min period of ischaemia of the isolated perfused rat heart. Without cardiac arrest the hearts only recovered 3% of their pre-ischaemic activity. With the progressive addition of various ions and chemicals recovery reached over 90%. Concentrations (mmol/L): potassium (K, 16); magnesium (Mg, 16); adenosine triphosphate (ATP, 10); creatine phosphate (CP, 10); procaine (7.4).
URL http://books.openedition.org/obp/docannexe/image/1982/img-3.jpg
Fichier image/jpeg, 64k
Légende Fig. 10.4 Hypothermia and ischaemic injury. Data from Hearse (1988). The graph shows the beneficial effects of hypothermia on the ischaemic heart. Rat hearts were subjected to 60 minutes of ischaemia at various temperatures. Their recovery was measured 15 minutes after the end of the ischaemic period and expressed as a percentage of the activity before ischaemia. Hypothermia produced good protection if the temperature was kept below 24° C.
URL http://books.openedition.org/obp/docannexe/image/1982/img-4.jpg
Fichier image/jpeg, 54k

Acheter

Rechercher dans OpenEdition Search

Vous allez être redirigé vers OpenEdition Search