The effects of cardioplegic and reperfusion conditions on energy metabolites and cardiac function were investigated in order to define better conditions for heart preservation (4 or 8 hrs). Myocardial energy metabolites (ATP, PCr and inorganic phosphate), intracellular pH and contractile function were followed using $\sp{31}$P NMR spectroscopy and left intra-ventricular balloon, respectively, during preservation and reperfusion in isolated pig and rat hearts. These hearts were subjected to various conditions of cardioplegia and reperfusion which involved re-arrest perfusion following ischemic preservation, increased concentrations of buffer and Mg$\sp{++}$ in cardioplegic and reperfusion solutions, and an intracellular-type cardioplegic solution. The effect of re-arrest perfusion was tested by comparing the recovery of energy metabolites and contractile function between pig hearts subjected to a secondary cardioplegic solution (S-C-S) prior to Krebs-Henseleit (K-H) solution and those reperfused with K-H solution alone after 8 hours of ischemic preservation at 12$\sp\circ$C. The levels of ATP and PCr during reperfusion in both groups of hearts were comparable whereas the left ventricular developed pressure was significantly higher in the hearts reperfused with S-C-S than in those reperfused only with K-H solution. The reperfusion-induced ventricular fibrillation that occurred in K-H reperfused hearts was prevented by re-arrest perfusion. A cardioplegic solution containing 150 mmol/L MOPS (higher buffer cardioplegic solution) helped to maintain intracellular pH during 8 hours of ischemic preservation. However, it did not affect the levels of energy metabolites during preservation and contractile function during reperfusion. The effects of 16 mmol/L Mg$\sp{++}$ in cardioplegic and reperfusion solution were evaluated using both rat and pig hearts. In working rat hearts, 16 mmol/L Mg$\sp{++}$ in cardioplegic solution did not alter myocardial oxygen consumption and contractile function following 30 minutes of normothermic preservation. Moreover, Langendorff pig hearts preserved with either 0 or 16 mmol/L Mg$\sp{++}$ cardioplegic solution showed similar decrements in energy metabolites during 4 hours of ischemic preservation at 12$\sp\circ$C and recovery of contractile function during reperfusion while 16 mmol/L Mg$\sp{++}$ in K-H solution resulted in a dramatic decline of contractile function. Furthermore, 16 mmol/L Mg$\sp{++}$ in S-C-S also did not affect the levels of high energy phosphates and contractile function during reperfusion. At 4$\sp\circ$C the pig hearts stored with either University of Wisconsin solution (UW, an intracellular-type cardioplegic solution) or St Thomas' solution (an extracellular-type cardioplegic solution) showed comparable changes in energy metabolites during 8 hours of preservation and a similar recovery of contractile function during reperfusion. However, at 12$\sp\circ$C, hearts stored in UW solution showed rapid decrease in ATP and PCr during preservation and significantly poorer functional recovery during reperfusion; four of eight hearts stored in UW solution at 12$\sp\circ$C showed the "stone heart" phenomenon with disappearance of PCr and ATP upon reperfusion. The addition of 0.5 mmol/L Ca$\sp{++}$ to UW solution significantly improved contractile function and prevented the occurrence of the "stone heart" phenomenon with stable levels of high energy phosphates. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/9571 |
| Date | January 1994 |
| Creators | Tian, Ganghong. |
| Contributors | Biro, George, |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 215 p. |
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