An assessment of crystalloid solutions for donor heart preservation.

The optimal technique for donor heart protection remains controversial. One component of preservation is the transport solution. Although saline solution is most frequently used as a transport medium, other crystalloid solutions may be superior. Accordingly, human right atrial trabeculae contracting isometrically in vitro were used to assess five crystalloid solutions at two different temperatures (12 degrees and 4 degrees C): St. Thomas' Hospital solution, modified Krebs-Henseleit (K+ = 16 mEq/L), Krebs-Henseleit (K+ = 4.5 mEq/L, saline, and Euro-Collins. After a 24-hour preservation period the muscles were restimulated at 34 degrees C and recovery of function was monitored for 30 minutes. Recovery of developed force was not affected by temperature (p = 0.13 by two-way analysis of variance). However, St. Thomas' Hospital solution provided the best recovery of developed force (103.3 +/- 6.2% of control) compared with saline, which had the worst developed force (2.8% +/- 1.3%) (p less than 0.002). Modified Krebs-Henseleit, Krebs-Henseleit, and Euro-Collins demonstrated intermediate performance. Although there were no differences between groups in recovery of resting force, it was greater in all groups with muscles cooled to 4 degrees C (238.7% +/- 17.6% of control) (p less than 0.001). Dry/wet weight ratios did not demonstrate statistically significant differences between groups. We conclude that, of the solutions tested, St. Thomas' Hospital solution provides the best preservation of atrial myocardium. Storage in crystalloid solutions leads to impaired relaxation, which is more apparent in tissue cooled to 4 degrees C and does not appear to be solely due to increased tissue swelling.

The human atrial trabecula: effects of calcium and temperature.

The human atrial trabecular preparation is an in vitro model which has been used to evaluate drugs and conditions to which cardiac muscle is exposed perioperatively. During its development, modifications have been made to this preparation. Two important components affecting myocardial muscle contraction are temperature and calcium concentration of the muscle bath medium. Previously, these parameters were determined independently of one another and found to be 34 degrees C and 2.5 mM calcium in a minimal Tyrode's buffer with glucose. This study was undertaken to define the optimal temperature and calcium concentration which would result in the highest yield of muscles that satisfied rigorous criteria for acceptability: developed force (DF) greater than 0.8 g, resting force (RF) less than 0.7 g, cross-sectional area less than or equal to 1.0 mm2). A total of 134 trabeculae were tested using a modified Krebs-Henseleit buffer, enriched with Eagles' medium and containing either 1.25 or 2.5 mM calcium at 34 or 37 degrees C. The trabeculae contracting in 2.5 mM calcium at 37 degrees C resulted in the highest yield of 26% while those maintained at 34 degrees C in either 1.25 or 2.5 mM calcium led to 20 and 15% useful preparations respectively (P = N.S.). Trabeculae contracting at 37 degrees C in 1.25 mM calcium resulted in the poorest yield of 8% (P = 0.002). There is a small (5 to 7%), but significant (P = 0.02), decrease in DF in 1 h when all groups were analyzed together. The exclusion criteria which are applied eliminate variability due to disease and/or treatment, therefore only 20 to 25% are acceptable for study. In summary, with well-defined and stringently applied criteria, the human right atrial trabecular preparation can be a reliable and reproducible model functioning at 37 degrees C and 2.5 mM calcium for a variety of studies.

The effect of mono(2-ethylhexyl)phthalate on an isolated perfused rat heart-lung preparation.

Di(2-ethylhexyl)phthalate (DEHP), the plasticizer used in the biomedical production of blood storage bags, hemodialysis systems, cardiopulmonary bypass (CPB) circuitry, and intubation tubes, is extracted from the plastic material when it comes into contact with biological fluids and is converted to its principal metabolite, mono(2-ethylhexyl)phthalate (MEHP). We have shown that MEHP causes cardiac and respiratory arrest, as well as hypotension, when infused into anesthetized rats. Using a well-ventilated in vitro rat heart-lung preparation, we investigated the effect of MEHP on pulmonary artery pressure (PAP) and found that MEHP had a hypertensive effect on the pulmonary vasculature ending in constriction and edema. There was a significant increase of 0.58 mm Hg/min in the PAP of isolated rat lungs when perfused with MEHP dissolved in Krebs-Henseleit (K-H) buffer (p = 0.0003). The rat lungs that were perfused with K-H buffer only increased 0.094 mm Hg/min during the same perfusion time of 20 min. The water gained during this time was 0.22 g/min with MEHP in the buffer compared to 0.04 g/min with buffer alone. The pO2 in the effluent did not decrease during the perfusion time. The concentration of MEHP in the rat lungs after perfusion varied from 20 to 40 micrograms/g. Although the mechanism of action of MEHP on PAP is too complex to be fully elucidated by this model, the increase in PAP which we have demonstrated is significant and adds yet another toxic effect of this major metabolite of the ubiquitous plasticizer, DEHP.

Atropine inhibition of the cardiodepressive effect of mono(2-ethylhexyl)phthalate on human myocardium.

Di(2-ethylhexyl)phthalate (DEHP) is a commonly used plasticizer in polyvinylchloride (PVC)-derived plastic. Mono(2-ethylhexyl)phthalate (MEHP), the major metabolite of DEHP, had a reversible, concentration-dependent (15-200 micrograms/ml) negative inotropic effect on a human in vitro atrial trabecular isometric preparation with an IC50 of 85 micrograms/ml. When atropine (22-32 micrograms/ml) was included in the atrial preparation the IC50 was shifted to greater than 120 micrograms/ml, suggesting that MEHP acts in part through the cholinergic receptors.

Perioperative exposure to plasticizers in patients undergoing cardiopulmonary bypass.

Di(2-ethylhexyl)phthalate and its principal metabolite, mono(2-ethylhexyl)phthalate, are contaminants of blood that are extracted on contact with polyvinylchloride surfaces, such as blood collection bags and tubing used in cardiopulmonary bypass. In this study, levels of the two plasticizers were measured in patients who underwent coronary artery bypass grafting, orthotopic transplantation, implantation of the Jarvik 7-70 total artificial heart during bridge-to-transplant procedures, and in infants who underwent corrective operations for congenital defects. In all adult patients the levels of di(2-ethylhexyl)phthalate increased tenfold by the end of cardiopulmonary bypass, whereas the levels of mono(2-ethylhexyl)phthalate increased ninefold. In infants, levels of di(2-ethylhexyl)phthalate rose seven times by the end of bypass and mono(2-ethylhexyl)phthalate rose significantly as well. In most of the patients having coronary bypass, the two plasticizers declined to preoperative levels within 24 hours. However, in some of the patients having orthotopic transplantation and in those in whom the Jarvik 7-70 total artificial heart was used as a bridge to transplant, the levels were still detectable 120 hours postoperatively. Circulating levels of mono(2-ethylhexyl)phthalate are only 20- to 35-fold lower in patients undergoing cardiac operations than the level of mono(2-ethylhexyl)phthalate causing a 50% reduction in developed contractile force and arrhythmias in an in vitro human atrial trabecular preparation. This study shows that patients with multisystem failure and infants may be at risk for this acute exposure to mono(2-ethylhexyl)phthalate.