raffinose and Myocardial-Ischemia

Pinacidil solutions have been shown to have significant cardioprotective effects. Pinacidil activates both sarcolemmal and mitochondrial potassium-adenosine triphosphate (K(ATP)) channels. This study was undertaken to compare pinacidil solution with University of Wisconsin (UW) solution and to determine if the protective effect of pinacidil involved mitochondrial or sarcolemmal K(ATP) channels.. Thirty-two rabbit hearts received one of four preservation solutions in a Langendorff apparatus: (1) UW; (2) a solution containing 0.5 mmol/L pinacidil; (3) pinacidil with Hoechst-Marion-Roussel 1098 (HMR-1098), a sarcolemmal channel blocker; and (4) pinacidil with 5-hydroxydecanote, a mitochondrial channel blocker. Left ventricular pressure-volume curves were generated by an intraventricular balloon. All hearts were placed in cold storage for 8 hours, followed by 60 minutes of reperfusion.. Postischemic developed pressure was better preserved by pinacidil than by UW. This cardioprotective effect was eliminated by 5-hydroxydecanote and diminished by HMR-1098. Diastolic compliance was better preserved by pinacidil when compared with UW. This protection was abolished by the addition of 5-hydroxydecanote and moderately decreased by HMR-1098.. Our results support the superiority of pinacidil over UW after 8 hours of storage. The cardioprotective role of pinacidil is mediated primarily by the mitochondrial K(ATP) channel.

Topics: Adenosine; Allopurinol; Animals; Benzamides; Cardiotonic Agents; Coronary Circulation; Decanoic Acids; Drug Evaluation, Preclinical; Female; Glutathione; Heart; Heart Ventricles; Hydroxy Acids; Insulin; Ion Transport; Male; Membrane Proteins; Mitochondria, Heart; Myocardial Contraction; Myocardial Ischemia; Organ Preservation; Organ Preservation Solutions; Pinacidil; Potassium Channels; Pressure; Rabbits; Raffinose; Random Allocation; Sarcolemma; Tissue and Organ Harvesting; Ventricular Function, Left

Long duration ischemia in hypothermic conditions followed by reperfusion alters membrane transport function and in particular Na,K-ATPase. We compared the protective effect of two well-described cardioplegic solutions on cardiac Na,K-ATPase activity during reperfusion after hypothermic ischemia. Isolated perfused rat hearts (n = 10) were arrested with CRMBM or UW cardioplegic solutions and submitted to 12 hr of ischemia at 4 degrees C in the same solution followed by 60 min of reperfusion. Functional recovery and Na,K-ATPase activity were measured at the end of reperfusion and compared with control hearts and hearts submitted to severe ischemia (30 min at 37 degrees C) followed by reflow. Na,K-ATPase activity was not altered after 12 hr of ischemia and 1 hr reflow when the CRMBM solution was used for preservation (55 +/- 2 micromolPi/mg prot/hr) compared to control (53 +/- 2 micromol Pi/mg prot/hr) while it was significantly altered with UW solution (44 +/- 2 micromol Pi/mg prot/hr, p < 0.05 vs control and CRMBM). Better preservation of Na,K-ATPase activity with the CRMBM solution was associated with higher functional recovery compared to UW as represented by the recovery of RPP, 52 +/- 12% vs 8 +/- 5%, p < 0.05 and coronary flow (70 +/- 2% vs 50 +/- 8%, p < 0.05). The enhanced protection provided by CRMBM compared to UW may be related to its lower K+ content.

Topics: Adenosine; Allopurinol; Animals; Cardioplegic Solutions; Glutathione; Insulin; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Organ Preservation Solutions; Potassium; Protective Agents; Raffinose; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Temperature; Time Factors

University of Wisconsin solution (UW) provides effective heart preservation under hypothermic conditions, but it can be deleterious at warmer temperatures. Re-warming during the implantation of the graft may be a problem. This study examined the damaging effect of peri-operative warm ischemia in a transplant setting and recovery from such damage. The amelioration of damage by rinsing the graft before re-warming and transplantation was also examined.. Rat donor hearts were preserved for 2 hr (0 degrees C) as follows: Series A was preserved with colloid-free UW (MUW), St. Thomas' solution (ST), or calcium-supplemented MUW (MUW+Ca) followed by either transplantation or warming (22 degrees C) for 10 min before transplantation. Series B was preserved with MUW, rinsed with fresh MUW, ST, MUW+Ca, or low-potassium MUW before warming and transplantation. All heart isografts were transplanted heterotopically with an indwelling left intraventricular balloon-tipped catheter. Graft function was measured 1 and 7 days after transplantation.. Grafts re-warmed rapidly during implantation. Function (left ventricular developed pressure, contractility, and relaxation) was significantly and persistently diminished in MUW-preserved grafts subjected to additional warming before transplantation. Preservation with ST was less effective than MUW despite being unaffected by warming. Preservation with MUW+Ca and rinsing with fresh MUW or ST before re-warming allowed recovery of function within 7 days despite significantly diminished function on day 1.. This study demonstrated that an increase in the peri-transplant warm ischemic period was detrimental when hearts were preserved with MUW. Preservation with calcium-supplemented MUW or rinsing the heart with fresh MUW or ST before transplantation ameliorated this damage.

Topics: Adenosine; Allopurinol; Animals; Blood Pressure; Body Weight; Cardioplegic Solutions; Glutathione; Graft Survival; Heart Transplantation; Insulin; Male; Myocardial Contraction; Myocardial Ischemia; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Inbred Strains; Time Factors; Transplantation, Isogeneic

Topics: Allopurinol; Animals; Cardioplegic Solutions; Coronary Circulation; Disaccharides; Electrolytes; Energy Metabolism; Glutamates; Glutathione; Heart; Histidine; Mannitol; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Organ Preservation; Raffinose; Rats; Time Factors

To establish whether coronary perfusion with cardioplegic solutions results in better intraischaemic structural preservation of endothelial cells than of cardiomyocytes, we determined intraischaemic swelling of these two cell types in hearts differently arrested during global ischaemia at 5 degrees C. Cardiac arrest was induced in situ by aortic cross clamping or by additional coronary perfusion with various cardioplegic solutions. Parameters for cellular swelling were determined, i.e. barrier thickness of capillary endothelial cells and sum of the volume fractions (V(V)) of free sarcoplasm and mitochondria (V(VSp) + V(VMi)) in cardiomyocytes. In order to test the intraischaemic relative increase of cellular volume in both cell types, regression analyses were performed. The results show that the relative intraischaemic volume increase was similar in both cell types after perfusion with histidine-tryptophan-ketoglutarate solution, and significantly less pronounced in capillary endothelial cells after perfusion with University of Wisconsin solution. In hearts arrested with St. Thomas' Hospital solution, a significantly higher volume increase was determined in capillary endothelial cells. Thus, capillary endothelium does not generally show a higher structural preservation than cardiomyocytes during ischaemia. Instead, volume regulation in both types of cells depends on the type of cardioplegic solution used. These results should be taken into consideration in human transplantation medicine.

Topics: Adenosine; Allopurinol; Animals; Bicarbonates; Calcium Chloride; Capillaries; Cardioplegic Solutions; Cell Size; Dogs; Endothelium, Vascular; Female; Glucose; Glutathione; Heart Arrest, Induced; Humans; Insulin; Magnesium; Male; Mannitol; Microscopy, Electron; Mitochondria, Heart; Mitochondrial Swelling; Myocardial Ischemia; Myocardium; Organ Preservation Solutions; Potassium Chloride; Procaine; Raffinose; Sodium Chloride

Recent evidence indicates that hyperglycemia is an important risk factor for the development of cardiovascular disease. We tested the hypothesis that myocardial infarct size is related to blood glucose concentration in the presence or absence of ischemic preconditioning (PC) stimuli in canine models of diabetes mellitus and acute hyperglycemia. Barbiturate-anesthetized dogs were subjected to a 60-min period of coronary artery occlusion and 3-h reperfusion. Infarct size was 24 +/- 2% of the area at risk (AAR) for infarction in control dogs. PC significantly (P < 0.05) decreased the extent of infarction in normal (8 +/- 2% of AAR), but not diabetic (22 +/- 4% of AAR), dogs. Infarct size was linearly related to blood glucose concentration during acute hyperglycemia (r = 0.96; P < 0.001) and during diabetes (r = 0.74; P < 0.002) in the presence or absence of PC stimuli. Increases in serum osmolality caused by administration of raffinose (300 g) did not increase infarct size (11 +/- 3% of AAR) or interfere with the ability of PC to protect against infarction (2 +/- 1% of AAR). The results indicate that hyperglycemia is a major determinant of the extent of myocardial infarction in the dog.

Topics: Animals; Blood Glucose; Blood Pressure; Coronary Circulation; Diabetes Mellitus, Experimental; Dogs; Heart Rate; Hyperglycemia; Insulin; Ischemic Preconditioning; Myocardial Infarction; Myocardial Ischemia; Osmolar Concentration; Raffinose

Optimal preservation of donor hearts remains a significant concern during transplantation. Organ shortage led to an increase in the use of damaged hearts.. To study the effect of preservation solutions on recovery of myocardial metabolism and function after warm ischemia, 10 dogs underwent 30 minutes of warm global ischemia under cardiopulmonary bypass. The animals were then administered 1 liter of Celsior (5 dogs), an extracellular crystalloid solution or 1 liter of University of Wisconsin solution (5 dogs), cooled at 4 degrees C, followed by 60 minutes of cold preservation and 30 minutes of warm blood reperfusion. Interstitial myocardial pH and pO2 changes were measured. The left ventricle dP/dt was measured before and after the ischemic episode, as where creatine kinase, troponine T and lactate serum levels.. Tissue pH averaged 6.9+/-0.1, 6.2+/-0.1, 6.7+/-0.1 and 6.8+/-0.1 before and after warm ischemia, following the 60 minutes of cold preservation and the reperfusion period in animals treated with the Celsior solution, compared to 6.8+/-0.1, 6.4+/-0.1, 7+/-0.1 and 6.8+/-0.2 respectively in dogs treated with the University of Wisconsin solution (p<0.05). Oxygen tension in the myocardium averaged 36+/-8 mmHg before warm ischemia and 59+/-31 mmHg after in animals that received Celsior compared to 30+/-10 mmHg and 49+/-7 mmHg in dogs treated with University of Wisconsin (p>0.05). Global myocardial function decreased significantly following reperfusion compared to baseline in both groups of animals. The serum levels of creatine kinase, troponine T and lactate increased significantly during the experiment although there was no significant difference between the 2 groups.. Both preservation solutions (Celsior and University of Wisconsin) resulted in suboptimal recovery of myocardial function and metabolism when administered after a period of warm ischemia. Strategies to improve recovery of damaged donor hearts remain to be appropriately defined.

Topics: Acid-Base Equilibrium; Adenosine; Allopurinol; Animals; Creatine Kinase; Dogs; Energy Metabolism; Glutathione; Insulin; Lactic Acid; Myocardial Ischemia; Organ Preservation; Organ Preservation Solutions; Potassium Compounds; Raffinose; Temperature; Troponin T; Ventricular Function, Left

Continuous hypothermic perfusion of donor hearts may provide extra protection for long ischemic times and suboptimal donors. The aim of three separate studies was to assess the effect of continuous hypothermic perfusion during simulated donor heart storage and implantation.. In study 1 twelve isolated rat hearts underwent 10 minutes of normothermic ischemia to simulate the effect of brain death on the heart and 5 hours of cardioplegic arrest, using University of Wisconsin solution. Six hearts were statically stored in University of Wisconsin solution at 2 degrees C, and six were perfused with University of Wisconsin solution. To assess the effect of simulated implantation, in study 2 an additional 12 hearts were statically stored for 5.5 hours in University of Wisconsin solution, six of which were rewarmed to a mean of 16 degrees C over the last 30 minutes of arrest. To assess the effect of simulated perfusion, in study 3 during implantation 12 hearts were rewarmed to a mean of 16 degrees C over the last 30 minutes of arrest, during which time six were perfused with 2 degrees C solution.. Hearts perfused during storage demonstrated greater recovery of prearrest power, 85.8% +/- 1.8%, than hearts preserved by static storage, 72.7% +/- 3.0% (p < 0.01). The simulated warm implantation period reduced recovery of power from 68.3% +/- 5.1% to 40.2% +/- 2.0% (p < 0.001). Perfusion during warm implantation improved recovery to 61.8% +/- 3.9% (p < 0.01). In all experiments improved function was accompanied by improved metabolic energy status.. During the implantation period of heart transplantation the donor heart sustains injury that could amount to 50% of total ischemic injury. Continuous perfusion during the cold storage phase and during simulated implantation improves recovery of the donor heart.

Topics: Adenine Nucleotides; Adenosine; Allopurinol; Animals; Blood Pressure; Body Water; Brain Death; Cardiac Output; Cardioplegic Solutions; Cryopreservation; Energy Metabolism; Glutathione; Heart; Heart Arrest, Induced; Heart Transplantation; Insulin; Male; Myocardial Contraction; Myocardial Ischemia; Myocardium; Organ Preservation; Organ Preservation Solutions; Oxygen Consumption; Perfusion; Raffinose; Rats; Rats, Wistar; Rewarming

The study aims to determine a possible relationship between intracellular water, energy metabolism, functional recovery and membrane permeability, during and after hypothermic cardiac preservation. Isolated rat hearts were stored for 12 h at 4 degrees C with University of Wisconsin (UW), St Thomas Hospital (ST) and Krebs-Henseleit (KH) solutions, and were reperfused for 1 h. Cellular volumes were measured by 1H NMR of water and 59Co NMR of the extracellular marker cobalticyanide, and energetic profiles by 31P NMR spectroscopy. Storage in ST solution reduced ischemic swelling from 2.50 +/- 0.06 to 2.73 +/- 0.09 (P < 0.001 v 3.56 +/- 0.10 ml/g dry weight in KH), while UW solution caused cellular shrinkage to 2.12 +/- 0.08 ml/g dry weight. Intracellular ATP concentrations and pH values were higher in UW as compared to ST solution. At reperfusion, hearts stored in ST shrank while those stored in UW expanded, resulting in similar intracellular volumes. Storage with UW was superior to ST in post-ischemic function 65 +/- 5% (P < 0.01 v 49 +/- 4% with ST) and in recovery of ATP 46 +/- 3% (P < 0.001 v 25 +/- 4% with ST). Storage with both ST and UW solutions did not prevent interstitial edema. Sarcolemmal membrane integrity, as assessed by cellular swelling in response to a hypo-osmotic shock (210 mmol/l), was significantly improved by ST and UW solutions as compared to KH (P < 0.05). Creatine kinase efflux was reduced by ST and UW as compared to KH (P < 0.05), and by UW as compared to ST (P < 0.05). Coronary flow was higher following storage with UW than ST solutions. 66 +/- 6 and 45 +/- 4%, respectively (P < 0.01). According to these data, the beneficial effects of UW and ST solutions on hypothermic ischemic storage of rat hearts included prevention of cellular edema and preservation of sarcolemmal membrane integrity. It is concluded: (a) UW and ST solutions reduce ischemic and reperfusion cellular volumes: (b) both solutions, and UW in particular were efficient in preservation of membrane integrity: (c) prevention of cellular edema is not the single or main mechanism responsible for the improved preservation with UW and ST solutions.

Topics: Adenosine; Allopurinol; Animals; Bicarbonates; Calcium Chloride; Cell Membrane Permeability; Cryopreservation; Glutathione; Heart; Hot Temperature; Insulin; Intracellular Fluid; Magnesium; Myocardial Ischemia; Myocardial Reperfusion; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Raffinose; Rats; Rats, Sprague-Dawley; Sodium Chloride

Topics: Adenosine; Allopurinol; Animals; Antioxidants; Cold Temperature; Creatine Kinase; Free Radical Scavengers; Glutathione; Heart; Heart Transplantation; Insulin; Ischemic Preconditioning, Myocardial; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Organ Preservation Solutions; Perfusion; Polyethylene Glycols; Pregnatrienes; Raffinose; Rats; Rats, Wistar; Superoxide Dismutase; Time Factors

Topics: Adenosine; Allopurinol; Animals; Cardiac Output; Cardioplegic Solutions; Glutathione; Heart; Heart Rate; Hemodynamics; In Vitro Techniques; Insulin; Lactates; Male; Myocardial Ischemia; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Wistar; Systole; Time Factors

Topics: Adenosine Triphosphate; Allopurinol; Animals; Cardioplegic Solutions; Creatine Kinase; Glutathione; Heart; Heart Arrest; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Myocardial Ischemia; Myocardium; Organ Preservation; Phosphates; Phosphocreatine; Phosphorus; Purines; Raffinose; Rats; Time Factors

The hypothermic simple immersion technique has been widely used to preserve the donor heart for transplantation. However, there is still controversy as to which temperature provides the best protection against prolonged ischemia. The low molecular weight solutes within cells depress the freezing point to -0.6 degree C. In practice, however, most cells do not freeze internally unless they are cooled below -10 degrees C. We investigated the effects of subzero nonfreezing storage at -1 degree C on the preservation of myocardial metabolism and function.. Isolated Wistar rat hearts were subjected to 6 hours of preservation with the intracellular type University of Wisconsin solution; the hearts of the subzero group were preserved at subzero nonfreezing (-1 degree C) temperature, and the hearts of the control group were at 4 degrees C. Recovery of cardiac function, myocardial adenine nucleotides content, and myocardial water content were evaluated after preservation.. Subzero group resulted in significantly better aortic flow, cardiac output, and aortic systolic pressure than in the control group. Myocardial adenosine triphosphate, adenosine diphosphate, and total adenine nucleotides at end-storage were significantly better preserved in subzero group when compared with the control group. Myocardial water content at reperfusion significantly increased in the control group compared with the subzero group.. Storage in the intracellular type solution at subzero nonfreezing (-1 degree C) temperature as compared with 4 degrees C appears to prolong myocardial preservation with respect to the enhancement of postischemic functional recovery, preservation of myocardial adenine nucleotides during ischemia, and prevention of myocardial edema at reperfusion.

Topics: Adenine Nucleotides; Adenosine; Allopurinol; Animals; Body Water; Cryopreservation; Glutathione; Heart; Insulin; Male; Myocardial Ischemia; Myocardium; Organ Preservation; Organ Preservation Solutions; Perfusion; Raffinose; Rats; Rats, Wistar; Temperature

Single or multiple brief periods of regional or global ischemia and reperfusion prior to a prolonged ischemic insult showed cardioprotective effects. Although this phenomenon (ischemic preconditioning [IPC]) has been described in ischemic reperfusion models, the effect of IPC on heart preservation has not been previously reported. We, thus, investigated the effect of IPC on heart preservation. Hearts isolated from male Wistar rats (250-350 g) were mounted on a Langendorff apparatus to estimate baseline function (aortic flow, coronary flow, cardiac output, heart rate, systolic pressure, and rate pressure product). All hearts were divided into 5 groups. In groups 1 and 4, the hearts were subjected to 8 and 12 hr of preservation, respectively. The hearts in group 2 were subjected to a single 2.5-minute cycle of normothermic global ischemic episode (IPC) before 8 hr of preservation. In groups 3 and 5, the hearts were subjected to two 2.5-min IPC cycles and stored for 8 or 12 hr. The hearts were arrested with University of Wisconsin solution and stored at 4 degrees C. Following storage, the hearts were reperfused and measured postpreservative function to assess cardiac functional recovery. Lactate and troponin-T leakage in the coronary perfusate was also measured. In group 3, the treatment of two 2.5-min IPC cycles significantly increased cardiac output, but the treatment of single 2.5-min IPC cycle did not affect the result. In the extended preservation group (group 5), the recovery (%) of both coronary flow and cardiac output were significantly increased compared with group 4. Furthermore, lactate leakage was significantly reduced in groups 2 and 3. These results suggest that IPC improves cardiac functional recovery following simple cold storage and has cardioprotective effects in rat heart preservation.

Topics: Adenosine; Allopurinol; Animals; Glutathione; Hemodynamics; Insulin; Male; Myocardial Ischemia; Myocardial Reperfusion; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Wistar

This work evaluates the myocardial protective potential of potassium cardioplegia on ischaemically arrested and reperfused hearts by two cardioplegic solutions: the University of Wisconsin solution (UW) and the standard crystalloid solution of St. Thomas' Hospital (ST). Evaluation of myocardial preservation was based on creatine kinase and lactate releases and on high-energy phosphate preservation of isolated rabbit hearts after 4 hours' hypothermic ischaemia. A morphometric ultrastructural evaluation of mitochondria in cardiomyocytes was also performed. The hearts of 24 rabbits were normothermally perfused with oxygenated Krebs-Henseleit solution for 30 min (Langendroff preparation), and the baseline contractile performance and biochemical parameters were evaluated. The hearts were then arrested and stored in the cardioplegic solutions (12 UW and 12 ST) at 4 degrees C for 4 hours. The hearts were then rewarmed and reperfused with oxygenated Krebs-Henseleit solution for further 30 min. At the end of reperfusion, creatine phosphate and high energy phosphates were higher with UW (p < 0.05); creatine kinase release during reperfusion was significantly lower with UW both at 15 min (p < 0.01) and at 30 min (p < 0.05). Lactate release during the first 15 min of reperfusion was about doubled (p < 0.05) with respect to controls in both groups; at 30 min this increase had almost vanished (+8%) with UW but not with ST (+30%). Ultrastructural morphometry did not show any significant difference at the level of mitochondria between the two treatments. The results indicate, for UW, an improved myocardial preservation associated with relative retention of high-energy phosphates and higher recovery of mechanical function, accelerated metabolic recovery and reduced stress of cell membranes.

Topics: Adenosine; Allopurinol; Animals; Bicarbonates; Calcium Chloride; Cardioplegic Solutions; Creatine Kinase; Cryopreservation; Energy Metabolism; Glutathione; In Vitro Techniques; Insulin; Lactic Acid; Magnesium; Myocardial Ischemia; Myocardium; Organ Preservation Solutions; Phosphates; Potassium Chloride; Rabbits; Raffinose; Sodium Chloride; Time Factors

Isolated canine hearts were preserved for 12 h at 5 degrees C followed by normothermic reperfusion for 2 h. Dogs were divided into two groups: group 1 (n = 7) received a nondepolarizing preservation solution in multidose, and group 2 (n = 6) received single-flushed University of Wisconsin (UW) solution, both administered in multidose fashion. At the end of reperfusion, the myocardial adenosine triphosphate concentration and left ventricular systolic and diastolic function were preserved better in groupl than in group 2. Myocardial mitochondrial ultrastructural integrity was identical in the two groups. These results suggested that in a 12-h heart preservation, nondepolarizing solution administered in multidose fashion protects the myocardium from the deleterious effects of hypothermia and cardioplegia better than UW solution.

Topics: Adenine Nucleotides; Adenosine; Adenosine Triphosphate; Allopurinol; Animals; Cardioplegic Solutions; Dogs; Glutathione; Heart; Heart Arrest, Induced; Insulin; Mitochondria, Heart; Models, Animal; Myocardial Ischemia; Myocardium; Organ Preservation; Organ Preservation Solutions; Phosphocreatine; Raffinose; Reperfusion; Ventricular Function, Left

The effectiveness of the University of Wisconsin solution and the Collins' M solution for preservation of rat hearts was compared by examining histologic appearance, tissue water content, and mitochondrial respiratory functions after prolonged hypothermic storage and subsequent heterotopic transplantation. Survival of transplanted hearts after 5 days of reperfusion was markedly lowered by storage in Collins' M solution for 15 hours. Hearts stored in University of Wisconsin solution for 10 hours showed no increase in myocardial necrosis after 5 days of reperfusion, whereas hearts stored in University of Wisconsin solution for 15 hours and Collins' M solution for 10 and 15 hours showed a significant increase in tissue necrosis. University of Wisconsin solution reduced tissue swelling during hypothermic storage, whereas Collins' M solution did not cause such reduction. The yield of mitochondrial protein after reperfusion was significantly decreased by storage in either solution, especially after 15 hours in Collins' M solution. Mitochondrial oxidative phosphorylation was significantly inhibited by storage, especially by storage in Collins' M solution and subsequent reperfusion. These results indicate that myocardial injury, after prolonged ischemia and reperfusion, results in a decrease in functionally and structurally intact mitochondria that is dependent on preservation conditions. University of Wisconsin solution protects isolated hearts against ischemia and reperfusion injury possibly by preventing cellular and mitochondrial deterioration.

Topics: Adenosine; Allopurinol; Animals; Body Water; Cardioplegic Solutions; Cold Temperature; Glutathione; Graft Survival; Heart Transplantation; Hypertonic Solutions; Insulin; Male; Mitochondria, Heart; Myocardial Ischemia; Myocardium; Necrosis; Organ Preservation; Organ Preservation Solutions; Oxidative Phosphorylation; Raffinose; Rats; Rats, Inbred Lew

Contracture of the arrested myocardium during prolonged storage of the heart results in both systolic and diastolic dysfunction, and is a major limitation to extended preservation. We studied the effects of a reversible contractile inhibitor, 2,3-butanedione monoxime (BDM), on myocardial ischemic tolerance. Isolated rabbit hearts were flushed with University of Wisconsin (UW) solution with and without 30 mmol/L BDM and 1 mmol/L CaCl, stored at 4 degrees C for 24 hours, and subsequently reperfused for 60 minutes. Left ventricular pressure-volume relationships and adenine nucleotide content were determined before reperfusion. Left ventricular systolic pressure, diastolic volume, and adenine nucleotide content were measured after reperfusion. Hearts stored in UW solution underwent contracture and adenosine triphosphate (ATP) depletion during storage, and exhibited systolic dysfunction, impaired diastolic relaxation, and poor ATP regeneration upon reperfusion. The addition of calcium worsened contracture and ATP depletion (p < 0.005) and slightly improved function and ATP regeneration (p = not significant). Hearts stored in the presence of BDM experience no contracture during storage; ATP was preserved (10.7 versus 15.7 nmol/mg; p < 0.05), and left ventricular systolic pressure and ATP content recovered to 74% and 93% of control on reperfusion, respectively (p < 0.005). Left ventricular diastolic volume remained depressed, however, although less than with UW solution (0.87 versus 0.45 mL; p < 0.001). When both BDM and calcium were included in the UW solution, calcium-stimulated ATP hydrolysis and contracture were prevented, left ventricular systolic pressure returned to 87% of control, and left ventricular diastolic volume and ATP content returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenine Nucleotides; Adenosine; Allopurinol; Animals; Calcium Chloride; Compliance; Coronary Circulation; Diacetyl; Glutathione; Heart Rate; Heart Ventricles; In Vitro Techniques; Insulin; Myocardial Ischemia; Myocardium; Organ Preservation; Organ Preservation Solutions; Rabbits; Raffinose; Solutions

The effectiveness of the University of Wisconsin solution on extended myocardial preservation was examined in this study using phosphorus 31-nuclear magnetic resonance spectroscopy. Isolated perfused rat hearts were arrested and stored in four preservation solutions: group 1, modified Krebs-Henseleit solution; group 2, modified St. Thomas' Hospital solution; group 3, oxygenated modified St. Thomas' Hospital solution containing 11 mmol/L glucose; and group 4, University of Wisconsin solution. The changes in myocardial high energy phosphate profiles and the intracellular pH values were measured during 12 hours of cold (4 degrees C) global ischemia and 90 minutes of normothermic reperfusion. Following ischemia, the hearts were assessed for hemodynamic recovery and myocardial water content. During ischemia, adenosine triphosphate depletion was observed in all groups; however, after 5 hours of ischemia, the adenosine triphosphate levels were significantly higher in group 3 compared with the other groups (adenosine triphosphate levels at 6 hours in mumol/gm dry weight: group 3, 7.6; group 4, 3.2; group 2, < 1; p < 0.025). The tissue water content at the end of ischemia was lower with the University of Wisconsin solution compared with the modified St. Thomas' Hospital solution or the oxygenated modified St. Thomas' Hospital solution (in ml/gm dry weight: group 4, 3.0; group 2, 4.4; group 3, 3.9; p < 0.05). The adenosine triphosphate repletion during reperfusion was greater with the University of Wisconsin solution compared with the modified St. Thomas' Hospital solution or the oxygenated modified St. Thomas' Hospital solution (12 mumol/gm dry weight in group 4; 8.1 in group 2; 9.0 in group 3; p < 0.05). Similar findings were obtained for the recovery of left ventricular pressure (in percent of preischemic control: group 4, 70%; group 2, 42%; group 3, 52%; p < 0.01) and coronary flow (group 4, 61%; group 2, 49%; group 3, 49%; p < 0.05). These data suggest that preservation with the University of Wisconsin solution affords improved hemodynamic recovery, enhanced adenosine triphosphate repletion, and reduced tissue edema upon reperfusion; however, oxygenated St. Thomas' Hospital solution with glucose is associated with the preservation of higher myocardial adenosine triphosphate levels during prolonged cold global ischemia. In conclusion, these data indicate that the University of Wisconsin solution might improve graft tolerance of ischemia in clinical heart transp

Topics: Adenosine; Adenosine Triphosphate; Allopurinol; Animals; Bicarbonates; Body Water; Calcium Chloride; Cardioplegic Solutions; Glutathione; Heart; Hemodynamics; Hydrogen-Ion Concentration; Insulin; Magnesium; Magnetic Resonance Spectroscopy; Male; Myocardial Ischemia; Myocardium; Organ Preservation; Organ Preservation Solutions; Phosphocreatine; Phosphorus; Potassium Chloride; Raffinose; Rats; Rats, Sprague-Dawley; Sodium Chloride; Solutions; Treatment Outcome