US3450502A - Method of operating heart-lung apparatus - Google Patents

Description

United States Patent U.S. Cl. 23-258.5 4 Claims ABSTRACT OF THE DISCLOSURE Isotonic solutions of certain ethylene oxide-polypropylene glycol condensation products have been found to be extremely effective as priming agents in the heart-lung apparatus.

The present invention relates to an improved method of operating the heart-lung apparatus. More particularly, the present invention relates to the use of certain solutions of ethylene oxide-polypropylene glycol condensation products as priming agents in the heart-lung apparatus.

The heart-lung apparatus is an instrument which permits surgeons to by-pass both the heart and the lungs during operations. The instrument comprises two essential components, a pump and an oxygenator. The function of the instrument is to oxygenate and withdraw carbon dioxide from blood and to pump this blood into the arteries, thus substituting for both the heart and the lungs. Prior to patient hook-up, the heart-lung apparatus is primed with enough fluid to fill all working chambers, reservoirs, and tubing in the patient. Historially, blood plasma was employed as a priming agent for the heartlung apparatus. However, because of the high cost, scarcity and storage problems of blood plasma, the art has long been in need of a material which will perform as a substitute therefor. To be useful as a blood plasma substitute, a material must possess the following properties: 1) it must retain a sufficient molecular size to remain in the blood space, thus creating an osmotic pres sure great enough to retain the solvent (water) within the circulation, (2) it must be miscible with blood, (3) it must be non-antigenic, non-toxic, and non-pyretogenic, (4) it must not draw water from the cellular area of the body, (5) it must be readily available and stable under prolonged storage conditions, and (6) when no longer needed, it must be readily discharged from the body circulation. With such formidable requirements, it is little wonder that the art has not heretofore found any material which satisfactorily performs as a blood plasma substitute. This is so notwithstanding the fact that various materials such as salt solutions, gelatin derivatives, various proteins and derivatives thereof, mannitol, starch and dextrans have been investigated as blood plasma substitues. However, these materials all lack one or more of the above requirements, thereby rendering them not totally acceptable as blood plasma substitutes.

Now, in accordance with the present invention, it has been determined that certain solutions of ethylene oxidepolypropylene glycol condensation products may be effectively employed as priming agents in the heart-lung apparatus. It has been determined that by the process of the present invention, prolonged extracorporeal circulation may be carried out without any significant adverse effects. Thus, the process of the present invention comprises the improvement in the operation of the heartlung apparatus which comprises employing as a priming agent therefor an isotonic (isosmotic) solution containing from 0.375 to 1.5 millimoles/liter of a compound of the formula wherein a is an integer such that the hydrophobe base represented by (C H O) has a molecular weight of at least 950 and b is an integer such that the hydrophile portion represented by (C H O) constitutes from about 50% to 90% by weight of the compound. By the phrase isotonic or isosmotic solution is meant a solution having the same osmotic pressure as blood. This phrase is well known in the art. Illustrative soliutions which may be employed in the preparation of the blood plasma substitutes employed in the process of the present invention include saline (a solution of sodium chloride, containing 8.5 to 9.5 grams of salt in 1000 cc. of purified water), Ringers solution, Ringers lactated solution, Krebs- Ringers solution, and various sugar solutions.

As stated above, critical amounts of certain ethylene oxide-polypropylene glycol condensation products must be employed in the preparation of the blood plasma substitutes useful in the present invention. Generally, the isotonic solutions useful in the present invention will comprise from 0.375 to 1.5 millimoles/liter of the abovementioned ethylene oxide-polypropylene glycol condensation products. Compositions comprising amounts of products outside of the above-cited range have been found to be unacceptable blood plasma substitutes.

The condensation products which are operable in the present invention are prepared by condensing ethylene oxide with polypropylene glycol. A more detailed discussion of the preparation of these products is found in U.S. 2,674,619. To be useful in the present invention, the products must contain at least 50% by weight of ethylene oxide. Furthermore, the polyproylene glycol base must have a molecular weight of at least 950. It has been determined that products outside of these limits are not satisfactory blood plasma substitutes for various reasons. For example, a product containing less than 50% ethylene oxide is not sufficiently non-toxic to be useful whereas a product containing a hydrophobic base molecular Weight of less than about 950 has completely different physio-a1 properties, particularly with regard to solubility, than the products useful in the present invention.

Illustrative ethylene oxide-polypropylene glycol condensation products which may be employed in the preparation of the isotonic solutions useful in the present invention include:

(1) 4750 molecular weight polyol containing approximately by weight ethylene oxide,

(2) 3500 molecular weight polyol containing approximately 5 0% by weight ethylene oxide,

(3) 7800 molecular weight polyol containing approximately 80% by weight ethylene oxide,

(4) 7500 molecular weight polyol containing approxi mately 70% by weight ethylene oxide,

(5) 16,250 molecular weight polyol containing approximately 80% by weight ethylene oxide,

6) 13,330 molecular weight polyol containing approximately 70% by Weight ethylene oxide,

(7) 9500 molecular weight polyol containing approximately by weight ethylene oxide.

The following examples illustrate the nature of the invention. All parts are by weight unless otherwise stated.

Example I An isotonic solution was prepared by dissolving 0.4% by weight of a 7800 molecular weight polyol prepared by condensing ethylene oxide with a polypropylene glycol having a molecular weight of 1750, said polyol containing approximately 80% ethylene oxide in Ringers lactated (0.513 millimoles/liter). Ringers lactated is a solution of 570 to 630 mg. sodium chloride, 290 to 330 mg. sodium lactate, 18 to 22 mg. calcium chloride, and 27 to 33 mg. potassium chloride in each 100 cc. of distilled water. The solution was then employed as a priming agent in the heart-lung apparatus in the manner described in an article by A. C. Hymes, N. Norimotf, and A. P. Thal, entitled A Comparison Between Mannitol Solutions and Low Molecular Weight Dextran as a Perfusate in Extracorporeal Circulation, Surgery, 59: 414-420, March 1966.

Of the 29 dogs perfused with the above solution, 27 survived (93% survival) without complications. Perfusion flow rates were high, and arterial blood pH one hour postperfusion was normal (7.33:0.06). Urine production was unimpaired during and following perfusion. Plasma hemoglobin was low and averaged 30 mg. percent. Fifteen minutes post-perfusion blood volume was only 8% greater than the initial blood volume before perfusion. Following this procedure, all of the fluid within the heartlung apparatus (now mixed with blood) was returned to the animal. The high flow rates during perfusion indicate that the osmotic pressure of the solute (polyol) was great enough to retain the solvent (water) within the vascular space during the procedure.

Example H A solution containing 1.0 millimole/liter of a polyol having a molecular weight of about 16,250 and containing approximately 80% ethylene oxide prepared by the reaction of ethylene oxide with a polypropylene glycol having a molecular weight of 3250 was prepared by dissolving 16.25 grams of said polyol in liters of saline solution containing 9 grams of sodium chloride in 1000 cc. of water. The solution was then employed as a priming agent in the heart-lung apparatus as described in Example I. Of the ten dogs treated, nine survived. In addition, no adverse effects were noticed in the surviving dogs.

What is claimed is:

1. The improvement in the method of operating the heart-lung apparatus which comprises employing as priming agent therefor, an isotonic solution containing from 0.375 to 1.5 millimoles/liter of a compound of the formula wherein a is an integer such that the hydrophobe base represented by (C H O) has a molecular weight of at least compound of the formula wherein a is an integer such that the hydrophobe base represented by (C H O) has a molecular weight of from 1750 to 4000 and b is an integer such that the hydrophile portion represented by (CZHQO) constitutes by weight of the compound.

3. The method of claim 1 wherein the isotonic solution comprises from 0.375 to 1.5 millimoles per liter of lactated Ringers solution of a compound of the formula wherein a is an integer such that the hydrophobe base represented by (C H O) has a molecular weight of at least 950 and b is an integer such that the hydrophile portion represented by (C H O) constitutes from about 50% to by weight of the compound.

4. The method of claim 1 wherein the isotonic solution comprises from 0.375 to 1.5 millimoles per liter of saline solution of a compound of the formula 2 4 )b( a s )a( 2 4. )b wherein a is an integer such that the hydrophobe base represented by (C H O) has a molecular weight of at least 950 and b is an integer such that the hydrophile portion represented by (C H.,O) constitutes from about 50% to 90% by weight of the compound.

References Cited MORRIS O. WOLK, Primary Examiner.

BARRY S. RICHMAN, Assistant Examiner.

US. Cl. X.R.