Cardiac Explants Research Articles

Inhibition of platelet GPIIbIa in an ex vivo model of hyperacute xenograft rejection does not prolong cardiac survival time

Abstract: Discordant cardiac xenografts are rapidly rejected in a process characterized by platelet activation with microvascular thrombosis, termed hyperacute rejection (HAR). The fibrinogen receptor GPIIbIIIa is crucial for the formation of platelet aggregates and potentiates platelet adhesion to subendothelial matrix. We have studied the effects of a specific GPIIbIIIa antagonist (GPI 562) in an ex vivo working heart model using discordant porcine hearts perfused with fresh, heparinized human blood. Stable plasma GPI 562 inhibitory levels were confirmed by inhibition of human platelet aggregation in vitro. Biopsies from the left ventricle of rejected hearts were analyzed by immunopathology. Control porcine hearts (n=8) underwent HAR and ceased functioning at around 60 min. Hearts perfused with human blood containing GPI 562 at 0.5 μM (n=5) appeared to show an initial increase in coronary blood flow relative to controls, but neither this difference nor survival times of the hearts reached significance. Mean cardiac output values were 7.3 ml/g (SEM 2.5) in the experimental group and 5 ml/g (SEM 0.6) in the control group following 5 min of working mode and were comparable at other timepoints. Platelet counts in the perfusate were maintained in the presence of GPI 562, unlike the reduction of over 50% in control samples. Immunohistochemistry suggested decreased platelet vascular plugging as determined by P‐selectin staining in the GPI 562 group, with associated reduction in neutrophil adherence and fibrin deposition. The use of GPI 562 in this ex vivo model conferred no marked benefits with respect to cardiac function and explant survival despite some positive differences on histological comparison. Further studies of this agent, in association with modalities of complement inhibition, are warranted in other models of discordant xenograft rejection.

Twenty-Four-Hour Intermittent Perfusion Storage of the Isolated Rat Heart: II. Perfusion Pressure and Functional Preservation

This study investigated the effect of intermittent perfusion (IP) pressures on functional preservation of the cold-stored isolated rat heart. The heart was flushed with cardioplegic solution #11 with ethylene diaminetetraacetic acid and 2, 3-butanedione monoxime (CP-11EB), and stored at 0°C for 24 hr. During storage, the heart was intermittently perfused for 3 min at 10 and 17 hr of storage with 25°C oxygenated CP-11EB. The IP pressures studied were: 20, 30, 40, 50, 60, 70, 80, and 100 mm Hg. Poststorage recovery of function was assessed with 30 min of working reperfusion. Control function of the unstored heart was: aortic flow (AF), 51.3 ± 2.2 ml/min; coronary flow (CF), 25.8 ± 1.2 ml/min; cardiac output (CO), 77.7 ± 2.3 ml/min; work, 92.0 ± 4.9 g-m/min; and coronary vascular resistance (CVR), 2.64 ± .21 mm Hg-min/ml. Functional return in the 30, 40, 50, 60, 70, and 80 mm Hg groups was similar. Recovery in a representative group (60 mm Hg) was: AF, 52 ± 3%; CF, 41 ± 2%; CO, 48 ± 3%; work, 42 ± 3%; and CVR, 225 ± 10% of the control. The total IP volume in this group was 71.0 ± 1.7 ml; total lactate dehydrogenase (LDH) release during IP was 8.62 ± .37 units/g dry; and end-storage tissue lactate was 52.6 ± 6.4 μmole/g dry. As IP pressure decreased to 20 mm Hg, cardiac functional recovery declined significantly to AF, 35 ± 6%; CF, 33 ± 2%; CO, 34 ± 5%; and work, 27 ± 4% of control (P< .05 vs. 60 mm Hg group). The total IP volume decreased to 10.1 ± .9 ml, tissue lactate content rose to 87.1 ± 10.9 (P< .05 vs. 60 mm Hg group), but LDH release fell to 5.59 ± .46 (P< .05 vs. 60 and 100 mm Hg groups). When IP pressure increased to 100 mm Hg, cardiac function was depressed with AF recovered to 25 ± 3%; CF, 30 ± 3%; CO, 26 ± 3%; work, 21 ± 3%; and CVR, 294 ± 26% of control (P< .05 vs. 60 mm Hg group). IP volume increased to 100.7 ± 2.4 ml; total LDH release increased to 19.1 ± 1.2 (P< .05 vs. 60 mm Hg group), although tissue lactate (58.9 ± 3.9) was not different from the 60 mm Hg group. End-storage tissue wet/dry weight ratio and myocardial adenosine triphosphate content were not different among the 20, 60, and 100 mm Hg groups. In conclusion, IP has a broad pressure optimum ranging from 30 to 80 mm Hg for 24-hr hypothermic preservation of the rat cardiac explant.

Chronic congestive heart failure is associated with a phenotypic shift of intramyocardial endothelial cells.

There is evidence that patients with chronic congestive heart failure have endothelial cell-related abnormalities of the peripheral circulation and the coronary microvasculature. For that reason, we have studied the phenotypic expression of endothelial cells in hearts of patients with congestive heart failure. We studied cardiac explants (n = 19) and autopsy hearts (n = 5) of patients with chronic congestive heart failure caused by either a dilated cardiomyopathy (n = 12) or ischemic heart disease (n = 12) and compared them with normal hearts (n = 12). The antigenic expression obtained with several endothelial cell markers (factor VIII-related antigen, EN-4, Ulex europaeus agglutinin-1 (UEA-1), PAL-E, endoglin, and endothelin) and adhesion molecules (intercellular adhesion molecule [ICAM], vascular cell adhesion molecule [VCAM], or E-selectin) was compared by use of immunohistochemical techniques. On the basis of the initial findings, the number of PAL-E- and EN-4-positive vessels was counted. The incidence of PAL-E-positive vessels per area was quantified and related to the percentage of heart muscle cells and the total number of vessels per area. In control hearts, endothelial cells rarely were positive for PAL-E. In hearts of patients with ischemic cardiomyopathies, there was distinct staining with this marker. Hearts of patients with dilated cardiomyopathies showed a marked increase in the number of PAL-E-positive endothelial cells. Vessels with a muscular media were PAL-E-negative. Two-sample analysis revealed a statistically significant difference between hearts with dilated cardiomyopathies and ischemic cardiomyopathies (P < .01), between hearts with dilated cardiomyopathies and control hearts (P < .01), and between hearts with ischemic cardiomyopathies and control hearts (P < .01). Endoglin and ICAM were positive but nondiscriminating. Endothelin, VCAM, and E-selectin were negative. A phenotypic shift in endothelial antigen expression of the coronary microvasculature occurs in both ischemic hearts and hearts with dilated cardiomyopathies, as revealed by PAL-E, compared with control hearts. The change may relate to compensatory mechanisms in long-standing chronic heart failure.

Dilated cardiomyopathy is associated with an increase in the type I/type III collagen ratio: A quantitative assessment

The aim of this study was to quantify total collagen and the type I/type III collagen ratio and their localization in hearts with dilated cardiomyopathy. Patients with dilated cardiomyopathy have an increase in intramyocardial fibrillar collagen. Types I and III are the main constituents and have different physical properties that may affect cardiac compliance. Nineteen hearts with dilated cardiomyopathy were studied (17 cardiac explants, 2 hearts obtained at autopsy) and compared with reference hearts. Total collagen was determined by hydroxyproline analysis. Collagen types I and III were analyzed using the cyanogen bromide method and immunohistochemical analysis followed by microdensitophotometric quantification. Localization of collagen types I and III was established at the light and electron microscopic levels. Immunoelectron microscopy provided information regarding their localization. Total collagen and the collagen type I/type III ratio were increased in hearts with dilated cardiomyopathy (p < 0.05). Electron microscopy showed a diffuse increase in collagen fibrils in the endomysium; the perimysium showed an inhomogeneous increase. Collagen fibrils were thicker, and fibrous long-spacing collagen occurred in the endomysium. Immunoelectron microscopic findings confirmed an increase in type I collagen. Hearts with dilated cardiomyopathy have a statistically significant increase in the collagen type I/type III ratio. The changes occur in the endomysium and perimysium, although with differences in distribution. These changes in intramyocardial collagen may be clinically relevant because they may affect cardiac rigidity and, therefore, eventually may render the heart less compliant. Further studies are needed to evaluate at what point in the course of the disease these changes appear.

Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure.

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.

Deferoxamine Given at Reperfusion Improves Function of the Cold-Stored Rat Heart

In this study deferoxamine (DF), a strong iron chelator, was administered either before storage or during reperfusion, in an attempt to inhibit the iron-dependent hydroxyl radical production and improve the functional recovery of the cold-stored/reperfused cardiac explant. Excised rat hearts were flushed with Krebs-Henseleit buffer (KHB), arrested with a cardioplegic solution, CP11-EB, with or without DF, and immersion stored in CP11-EB at 0°C for 16 hr. To assess function, the stored hearts were reperfused in the working mode with KHB for 30 min. Experimental groups included: (i) DF treatment during prestorage flush [CP11-EB + 0.01 mM (n = 5), 0.05 mM (n = 13), 0.1 mM (n = 5), 0.2 mM (n = 5), or 0.75 mM DF (n = 5)]; (ii) DF treatment during reperfusion [KHB + 0.3 mM (n = 5), 0.6 mM (n = 7), 0.75 mM (n = 11), 1.0 mM (n = 6), 1.5 mM (n = 4), or 2.5 mM DF (n = 7)]; and (iii) untreated group (n = 8) received no DF during flush or reperfusion. Function of unstored hearts (n = 7) including aortic flow (AF, 54.6 ± 2.6 ml/min); cardiac output (CO, 76.5 ± 3.3 ml/min), systolic pressure (SP, 135.7 ± 1 mm Hg), diastolic pressure (DP, 70.7 ± 3.8 mm Hg), and work (96.7 ± 6.4 g-meter/min) served as controls. Functional recovery of the untreated group was AF, 59%; CO, 58%; SP, 71%; DP, 73%; work, 41% of control values. DF treatment at any dose during the initial flush did not improve functional recovery. In contrast, DF treatment (0.75 and 1.0 mM) during 30 min reperfusion produced significantly better function compared to the untreated group (P < 0.05). The functional recovery of the 0.75 mM group was AF, 71%; CO, 67%; SP, 76%; work, 52% of control. The functional recovery of the 1.0 mM group was CO, 68%; SP, 79%; DP, 82%; work, 55% of control. Shorter treatment with 0.75 mM DF for the first 5 (n = 7) or 10 (n = 9) min of reperfusion did not elicit the beneficial effect of DF. These results suggest that hydroxyl radical production at reperfusion may play a role in injury to the cold-stored/reperfused rat heart. Furthermore, this production may affect function for a period longer than the first few minutes of reperfusion.

Antifreeze Glycoproteins from Antarctic Notothenioid Fishes Fail to Protect the Rat Cardiac Explant during Hypothermic and Freezing Preservation

The antarctic notothenioid fishes avoid freezing through the action of circulating antifreeze glycoproteins (AFGPs). This study investigated whether AFGPs could serve as cryoprotectants for the isolated rat heart under three different storage conditions. (1) Hearts were flushed with 15 mg AFGP/ ml cardioplegic solution (CP) and stored for 9 h at 0°C. This AFGP concentration has been reported to protect pig oocytes during hypothermic storage. (2) Hearts were flushed with 10 mg AFGP/ml CP-14 and stored frozen at - 1.4°C for 3 h. At this concentration the AFGPs significantly reduce the solution freezing point and also change the crystal morphology from dendritic to spicular. (3) Hearts were flushed with 10 μg AFGP/ml CP-15 and stored frozen at - 1.4°C for 5 h. At this low concentration the AFGPs have a strong inhibitory effect on ice recrystallization, but have little effect on the freezing point and less apparent effect on the crystal habit. After hypothermic or freezing storage, the functional viability was assessed by determining cardiac output (CO) during working reperfusion. No difference in CO was found between AFGP-treated and untreated hearts after 9 h of 0°C storage. CO in hearts frozen in CP-14 without AFGPs recovered to 50% of the freshly perfused control hearts. Hearts frozen in the presence of high concentrations of AFGPs (10 mg/ml CP-14) failed to beat upon thawing and reperfusion, although their tissue ice content was less than that found in hearts without AFGP treatment. Hearts frozen with low concentrations of AFGPs (10 μg/ml CP-15) showed reduced recovery upon thawing and reperfusion compared to CP-15 hearts, which recovered to 67% of freshly perfused controls. Thus notothenioid fish AFGPs not only fail to enhance storage of the isolated rat heart preparation at hypothermic temperatures, but cause increased damage under freezing conditions regardless of AFGP concentration.

Graft vascular disease in the great vessels and vasa vasorum

To determine whether the great vessels were subject to transplantation-associated arteriosclerosis (graft vascular disease) we studied sections of aorta and pulmonary arteries from 19 cardiac explant cases. Sections of the same vessels from five autopsied hearts from patients who had received liver and/or kidney transplants with immunotherapy as well as from eight recipient hearts served as controls. In addition, eight donor hearts (three aortae and eight pulmonary arteries) that were not used for heart transplantation were examined. Intimal proliferation was noted in the aorta but affected the pulmonary arteries only slightly, whereas the vasa vasorum of both vessels were involved and were occluded or stenosed by thickened intima containing recanalized capillaries. On morphometric study the ration of intima to media in the aorta was significantly higher in the heart transplant group than in the control group (0.14 ± 0.14 [n = 19] v 0.02 ± 0.02 [n = 16]; P<.01). This intimal thickening was not correlated with the use of cyclosporine or with other clinicopathologic factors. The cytomegalovirus infection rate was higher in the heart transplant group (85%) than in the control group (40%).

Freezing preservation of the mammalian cardiac explant V. Cryoprotection by ethanol

We studied the colligative cryoprotective effect of ethanol (EtOH) in preserving the isolated rat heart frozen at −3.4 °C or unfrozen at −1.4 °C. Addition of 4.7% ( v v ) EtOH to a cardioplegic solution, CP-14, raised the osmolality from 280 to 1100 mOsm/kg H 2O and lowered the melting point from −0.52 to −2.1 °C. Freezing of the cardiac explant at −3.4 °C for 6 h resulted in 34.3 ± 1.9% of the tissue water as ice; recovery of cardiac output (CO) was 50%. Polyethylene glycol, which at 5% ( w v ) has been shown to cryoprotect the hearts during freezing at −1.4 °C, did not improve the protective effect of 4.7% EtOH. CP−14 + 4.7% EtOH did not freeze at −1.4 °C. After 6 h storage, CO in hearts flushed with CP-14 + 4.7% EtOH oxygenated with 95% O 2/5%CO 2 returned to almost control level and was much higher than that in hearts flushed with 100% O 2 saturated-CP−14 + 4.7% EtOH. Storage of 8 and 12 h reduced CO to 87 ± 9 and 60 ± 5% of control. By employing EtOH as a colligative cryoprotectant, we preserved the adult mammalian heart frozen at −3.4 °C or unfrozen at −1.4 °C, suggesting that this small molecular weight, penetrating substance may be a suitable cryoprotectant for long-term storage of the cardiac explant at high subzero temperatures.

Freezing preservation of the mammalian cardiac explant VI. Effect of thawing rate on functional recovery

This study investigated the effect of thawing rate on the preservation of frozen isolated rat hearts. The hearts were flushed with a hyperosmotic cardioplegic solution, CP-14/EtOH (1.15 Osm/kg), frozen at a rate of 0.18 °C/hr for 6 h to −3.2 °C. Thereafter, the hearts were thawed at rates ranging from 0.08 to 1.1 °C/min for 1 to 14 min until the heart temperature reached −2.1 °C, the melting point (MP) of the flush solution; then they were held at −1 °C for 11 to 24 min so that the total thaw time was 25 min. Post-thaw function was assessed by working reperfusion and expressed as percentage of unstored control function. Cardiac output (CO) and other hemodynamic performance showed biphasic responses to the thaw rate. At 0.08 °C/min rate, CO recovered to 29.1 ± 4.1 ml/min (40.8 ± 5.8% of control). Thawing at 0.13 °C/min enhanced the recovery of CO to 60.5 ± 4.9%. Between 0.13 and 0.34 °C/min, recovery was statistically insignificant. Faster thawing at 0.59 and 1.1 °C/min caused progressively less recovery. Overall, 0.13 °C/min offered the highest recovery. In conclusion, function in slowly frozen heart is intimately affected by the thawing rate; there was an optimal intermediate thawing rate and both too slow and too fast thawing were detrimental.

Paradoxical effect of cerium on collagen synthesis in cardiac fibroblasts

The present study examined the effect of cerium on collagen synthesis in cultured cardiac fibroblasts and explants. At 100 n m, a concentration comparable with that found in the cardiac tissue of patients with endomyocardial fibrosis, the element was found to enhance the incorporation of tritiated proline into collagen and non-collagen proteins while at 10 μ m, it had an inhibitory effect. Cerium was found to have no effect on rates of DNA synthesis in fibroblasts at 100 n m. However, at this concentration, the element markedly enhanced the incorporation of tritiated uridine into RNA, suggesting that cerium may act at the level of transcription to stimulate collagen and non-collagen protein syntheses. The stimulatory action of very low levels of cerium on collagen synthesis may contribute to the accumulation of collagen seen in endomyocardial fibrosis.

Freezing preservation of the mammalian cardiac explant. II. Comparing the protective effect of glycerol and polyethylene glycol

We compared the cryoprotective ability of glycerol and polyethylene glycol (PEG) during freezing. Isolated rat hearts were flushed with one of three cardioplegic solutions (CP-14, CP-15, and CP-16), frozen at −1.4 °C, and reperfused after thawing to assess function. After 3 h freezing, cardiac output (CO) in CP-14-flushed hearts recovered to 58.1% of control. CP-16 (CP-14 with 5% PEG) improved CO to 77.5%. Five hours of freezing abolished recovery in CP-14 hearts, but CP-15 (CP-14 with 50 m M glycerol) and CP-16 hearts produced 40.0 and 49.0% CO, respectively. With 6 h freezing, CP-15 hearts did not recover, whereas CP-16 hearts recovered 37.5% CO. In CP-14 hearts frozen for 3 h, 37.4% of the tissue water was ice that increased to 44.7% with 5 h freezing. CP-15 and CP-16 hearts had 34.4 and 30.9% tissue ice, respectively, after 5 h freezing. Tissue water contents in CP-14 and CP-15 hearts (3.83 to 3.96 g H 2O g dry) were 14 to 24% higher than that in CP-16 hearts. Six hours of freezing elevated AMP and ADP contents and reduced ATP levels in CP-15 and CP-16 hearts. Total adenine nucleotide (TAN) content of CP-15 hearts was 72% of control, while that of CP-16 hearts was normal. In conclusion, both glycerol and PEG offered cryoprotection by reducing tissue ice formation. PEG was superior by reducing tissue ice content further via dehydration and by better preserving TAN Content.

Tissue ice content and function recovery of the cardiac explant after freezing

Tissue ice content and function recovery of the cardiac explant after freezing

Chronic non-ischaemic congestive heart disease and endoniyocardial biopsies. Worth the extra?

The diagnostic yield of endomyocardial biopsies in patients with chronic congestive heart failure of non-ischaemic aetiology remains questionable and, therefore, the use of endomyocardial biopsies under such circumstances is at stake. The present report documents the correlation between the histologic interpretation of endomyocardial biopsies and the corresponding cardiac explants in 13 patients who underwent cardiac transplantation. The biopsy diagnoses in these patients varied from 'compatible with dilated cardiomyopathy' (n = 6) to 'non-conclusive' (n = 4), 'ischaemia' (n = 2) and 'borderline myocarditis' (n = 1). Correlation with the corresponding cardiac explants revealed hypertrophy of myocytes as the leading histologic feature in the majority of cases. Because of the non-specific histopathology of dilated cardiomyopathy, the discrepancy between biopsy diagnoses and the leading explant diagnosis is mostly a matter of semantics. Ischaemia was present at high incidence, but is considered a result of imparied myocardial perfusion rather than the prime mechanism of heart failure. In four cardiac explants myocarditis was encountered, while the corresponding biopsies showed no cellular inflammation. In two, the cellular infiltrates suggested an early state of repair. One heart contained an active and extensive lymphocytic myocarditis. The fourth case showed an eosinophilic myocarditis, most likely acquired after the biopsy was taken. These discrepancies almost certainly relate to the sampling error and the time interval between biopsy and onset of symptoms. The immediate diagnostic yield of the biopsy, in this particular subset of patients, was minimal, particularly with respect to the diagnosis 'myocarditis'. Nevertheless, biopsy diagnoses such as 'compatible with' and 'non-conclusive' do contribute to the final categorization and management of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of fibronectin, laminin, and galactosyltransferase adhesion mechanisms during embryonic cardiac mesenchymal cell migration in vitro

Embryonic hearts contain a homogeneous population of mesenchymal cells which migrate through an extensive extracellular matrix (ECM) to become the earliest progenitors of the cardiac valves. Since these cells normally migrate through an ECM containing several adhesion substrates, this study was undertaken to examine and compare three ECM binding mechanisms for mesenchymal cell migration in an in vitro model. Receptor mechanisms for the ECM glycoproteins fibronectin (FN) and laminin (LM) and the cell surface receptor galactosyltransferase (GalTase), which binds an uncharacterized ECM substrate, were compared. Primary cardiac explants from stage 17 chick embryos were cultured on three-dimensional collagen gels. Mesenchymal cell outgrowth was recorded every 24 hr and is reported as a percentage of control. Migration was perturbed using specific inhibitors for each of the three receptor mechanisms. These included the hexapeptide GRGDSP (300–1000 μg/ml), which mimics a cell binding domain of FN, the pentapeptide YIGSR (300–1000 μg/ml), which mimics a binding domain of LM, and α-lactalbumin (1–10 mg/ml), a protein modifier of GalTase activity. The functional role of these adhesion mechanisms was further tested using antibodies to avian integrin (JG22) and avian GalTase. While the FN-related peptide had no significant effect on cell migration it did produce a rounded cellular morphology. The LN-related peptide inhibited mesenchymal migration 70% and α-lactalbumin inhibited cell migration 50%. Antibodies agasinst integrin and GalTase inhibited mesenchymal cell migration by 80 and 50%, respectively. The substrate for GalTase was demonstrated to be a single high molecular weight substrate which was not LM or FN. Control peptides, proteins and antibodies demonstrated the specificity of these effects. These data demonstrate that multiple adhesion mechanisms, including cell surface GalTase, are potentially functional during cardiac mesenchymal cell migration. The sensitivity of cell migration to the various inhibitors suggests that occupancy of specific ECM receptors can modulate the activity of other, unrelated, ECM adhesion mechanisms utilized by these cells.

Long-term storage of the cardiac explant from rats of different thyroid states

Long-term storage of the cardiac explant from rats of different thyroid states

Optimal osmolality for cold storage of the cardiac explant

Cell swelling is a major problem of cardiac preservation. This study evaluated the effect of storage solution osmolality on long-term preservation of cardiac function. Isolated rat hearts were flushed and stored in solutions of 260 to 350 mOsm/kg water at 0°C for 9 hr. Cardiac performance was assessed using the isolated working heart reperfusion. Function of fresh unstored hearts served as the control. The stored hearts had normal heart rate after reperfusion. Other hemodynamic functions recovered to various levels of the control value and showed biphasic responses to solution osmolality. Hearts stored in hyposmotic (260 and 270 mOsm) and hyperosmotic (310, 330, and 350 mOsm) solutions performed poorly. Those stored in 280 to 290 mOsm solutions showed superior recovery in cardiac function. Among all parameters, coronary flow correlated linearly with aortic flow, cardiac output, systolic pressure, work, oxygen consumption, and coronary vascular resistance. Solutions of 280, 290, and 310 mOsm caused 6 to 9% increases in tissue water (TW) over the control hearts during 9 hr storage, whereas 350 mOsm solution maintained TW at the control level. After reperfusion, all stored hearts gained water (25 to 38%) compared to hearts with no reperfusion. Postreperfusion myocardial ATP content was only 70–79% of control level and did not correlated to function recovery. In conclusion, (1) the optimal osmolality of our preservation fluid is 280 to 290 mOsm and moderate or severe hyperosmolality is detrimental to cardiac function, and (2) preservation of coronary function may be crucial to future improvement of storage solution.

Evaluation of pH buffer systems for long-term storage of the cardiac explant

Evaluation of pH buffer systems for long-term storage of the cardiac explant

31P nuclear magnetic resonance (NMR) study of the cardiac explant stored at 0°C

31P nuclear magnetic resonance (NMR) study of the cardiac explant stored at 0°C

The effect of buffer and pH on hypothermic storage of the cardiac explant: T. Wang, P.R. Batty, G.L. Hicks, J.A. DeWeese. Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA

The effect of buffer and pH on hypothermic storage of the cardiac explant: T. Wang, P.R. Batty, G.L. Hicks, J.A. DeWeese. Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA