| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1998;66:1953-1957
© 1998 The Society of Thoracic Surgeons
a King Fahad National Guard Hospital, Riyadh, Saudi Arabia
Accepted for publication May 28, 1998.
Address reprint requests to Dr Landymore, Department of Cardiac Sciences, King Fahad Hospital, P.O. Box 22490, Riyadh, Saudi Arabia
Presented at the Canadian Cardiovascular Society, Montreal, Quebec, Canada, October 29–November 2, 1996.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsCommentReferences |
|---|
Methods. Preconditioning was achieved with 5 minutes of global ischemia followed by 10 minutes of reperfusion. The heart was then arrested with 1 L of crystalloid cardioplegia, explanted, stored in a transport cooler, and then transplanted into recipient sheep. The total ischemia time was 2 hours. Pressure-volume loops were used to calculate preload recruitable stroke work, the maximum elastance, and diastolic compliance. Linear regression analysis was used to determine the preload recruitable stroke work, maximum elastance, and diastolic compliance–and end-diastolic volume relationship. The area under the regression curve for preload recruitable stroke work was defined as the preload recruitable stroke work area. Biopsies were taken for high-energy phosphates.
Results. Systolic function, represented by preload recruitable stroke work area, was preserved after cardiac transplantation in preconditioned animals. Maximum elastance and diastolic compliance were unaffected by preconditioning or ischemia. High-energy phosphates were better preserved in preconditioned animals.
Conclusion. Preconditioning prevented myocardial stunning and preserved high-energy phosphates after experimental cardiac transplantation.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
Surgical preparation
The animals were anesthetized and prepared for cardiopulmonary bypass. The surgical preparation and instru-mentation has been described in detail in a previous publication [8].
Hemodynamic measurements
Systolic and diastolic function were determined by simultaneous measurement of left ventricular pressure and volume [9]. A detailed description of the pressure-volume catheters was published previously [8]. Preload recruitable stroke work (PRSW), the maximum elastance (Emax), and diastolic compliance (DC) were automatically calculated from pressure-volume loops with specially designed software. The PRSW was indexed to body weight.
Hemodynamic measurements were made during rapid volume loading. The measurements were made before cardiac transplantation and repeated at 90 minutes and 150 minutes after releasing the aortic cross-clamp (Fig 1). Linear regression analysis of PRSW and end-diastolic volume (EDV) was used to determine the PRSW-EDV relationship. Preload recruitable stroke work area (PRSWA) was defined as the area under the regression curve [10] and was calculated from the following formula: 
where Msw represents the slope of the regression curve and Vsw represents the X intercept. End-diastolic volume was extrapolated to 50 mL (EDV50). Maximum elastance (Emax) was regressed against EDV and extrapolated to an EDV of 50 mL so that the measurements could be compared between groups under a similar loading condition. Diastolic compliance was regressed against EDV to determine the DC-EDV relationship. DC was extrapolated to an EDV of 50 mL.
|
Preconditioned group
Nine sheep were anesthetized and cannulated for the initial hemodynamic measurements. After completing the initial assessment, the animals were placed on bypass at 37°C and then immediately cross-clamped. After 5 minutes of global ischemia, the clamp was removed and the heart reperfused for 10 minutes. The heart was then arrested with 1 L of crystalloid cardioplegia, explanted, and placed in a transport cooler. Seventy-five minutes later the heart was transplanted into a recipient sheep. The cross-clamp was removed after a total of 2 hours of ischemia. After 1 hour of reperfusion, the animals were weaned from cardiopulmonary bypass.
Surgical technique
The heart transplantation was performed using the technique originally described by Lower and Shumway [12]. Inotropic support was not used in any of the transplant recipients. Blood gases were monitored and maintained within normal limits.
High-energy phosphates
Biopsy specimens were obtained with a Tru-Cut biopsy needle (Travenol Laboratories, Deerfield, IL) before cardiac transplantation, and at 90, 120, and 150 minutes after releasing the aortic cross-clamp (Fig 1). The samples were immediately placed in liquid nitrogen. High-performance liquid chromatography was used to determine the concentrations of adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate [13]. The measurements have been reported as µmol/g (dry weight).
Statistical methods
The results are reported as the arithmetic mean ± the standard error of the mean. Analysis of variance was used for the analysis of the hemodynamic data and the Student’s t test was used to analyze the measurements of high-energy phosphates.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
After cardiac transplantation and release of the aortic cross-clamp, ventricular fibrillation occurred spontaneously in both groups. The heart, however, was defibrillated without difficulty in all animals on the first or second attempt and without the need for lidocaine. The animals were weaned from cardiopulmonary bypass without the use of calcium or inotropic support and survived the period of reperfusion until the end of the protocol. Hemoglobin during reperfusion measured 70 ± 0.2 g/L in the control group and 69 ± 0.4 g/L in the preconditioned animals.
Preload recruitable stroke work area
Preload recruitable stroke work area (PRSWA) is illustrated in Table 1. It was similar in both groups before cardiac transplantation. However, 90 minutes after ischemic arrest, PRSWA was significantly lower in the control group (p < 0.04). In contrast, systolic function was not affected by cold hypothermic storage in the animals that had been preconditioned; PRSWA was somewhat higher in comparison with the pretransplantation assessment. The trend continued to 150 minutes after release of the aortic cross-clamp; PRSWA was significantly higher in the preconditioned animals (p < 0.02) compared with the control group. Not only was PRSWA lower during reperfusion in the control group but it failed to recover during the period of observation. The slight increase in PRSWA observed in the preconditioned group after transplantation did not represent an absolute increase in mechanical function but rather preservation of systolic function, which is often decreased after cold cardioplegic arrest.
|
|
|
|
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
Although previous preconditioning protocols described the use of three or four periods of ischemia alternating with reperfusion [1, 2], it is now recognized that a single episode of ischemia, lasting no more than 5 minutes, will precondition the myocardium [14]. The beneficial effects of preconditioning, however, are attenuated when coronary artery occlusion is preceded by 40 to 65 preconditioning cycles [15]. The delay between the preconditioning protocol and the period of coronary artery occlusion might also be a limiting factor. Li and Kloner [16] reported that the preconditioning effect is lost if the delay between preconditioning and the sustained period of ischemia exceeds 60 minutes. Lastly, preconditioning might be ineffective if the duration of coronary artery occlusion exceeds 90 minutes [17]. With these limitations in mind, the preconditioning protocol for this experimental investigation consisted of a single 5-minute period of global ischemia followed by 10 minutes of reperfusion with the total duration of ischemia limited to 2 hours.
Systolic function was assessed in this experimental model of cardiac transplantation by measuring PRSWA. Preload recruitable stroke work was measured during rapid volume loading, and linear regression was used to determine the PRSW-EDV relationship. Systolic function was represented by the area under the regression curve. Because this measurement is independent of preload and heart rate, the relationship is one of the best overall assessments of left ventricular function [10]. In contrast, isolated measurements of Emax or the maximum rate of increase in left ventricular pressure (Dp/Dt) might not accurately assess left ventricular function, particularly under conditions of myocardial ischemia [18]. Measurements of Emax reported here emphasize the shortcomings of assessing isolated, preload-dependent measurements of left ventricular function, as Emax was unaffected by cardiac transplantation, an observation that is highly questionable considering that the myocardium had been subjected to 2 hours of ischemia. Assessment of PRSWA after transplantation demonstrated decreased systolic function in the control group but preserved function in the animals that had been preconditioned. We demonstrated that preconditioning prevents the stunning effect of cold storage and ischemia that invariably is observed after transplantation.
Preconditioning not only preserved systolic function after transplantation but reduced the depletion of adenosine triphosphate and its precursors. Adenosine triphosphate and its precursors were well preserved in the animals that had undergone preconditioning. In contrast, adenosine triphosphate was significantly reduced at 90 and 120 minutes in the control group. The failure of adenosine triphosphate to be regenerated during reperfusion in the control group, despite relatively normal levels of precursors, indicates that hypothermic mitochondrial dysfunction was present in the nonpreconditioned animals after cold cardioplegic arrest [19]. Our observations lend support to earlier observations in isolated rat hearts [14, 20] and patients undergoing coronary artery bypass operations [3].
This investigation used preconditioned hearts for experimental cardiac transplantation. There have been several studies that examined the effects of preconditioning and myocardial storage on myocardial recovery in isolated heart preparations. Saitoh and colleagues [21] recently reported that rat hearts preconditioned with two 2.5-minute episodes of global ischemia separated by 10 minutes of reperfusion demonstrated improved functional and metabolic recovery after 8 to 12 hours of storage in University of Wisconsin solution. Valen and associates [22], using a Lagendorff model, preconditioned rat hearts with two 3-minute episodes of ischemia followed by 5 minutes of reperfusion. Diastolic function was better preserved in the preconditioned hearts subjected to warm ischemia but not in hearts stored for 3 to 3.5 hours between 6°C and 8°C. In contrast, Ogino and colleagues [23] have shown that 5 minutes of global ischemia and 10 minutes of reperfusion, preceding 6 hours of cold (4°C) storage, preserved diastolic function. Lastly, Karck and colleagues [24] subjected isolated, working rat hearts to 5 minutes of global ischemia followed by 5 minutes of reperfusion. The hearts were then stored at 4°C for 10 hours in five preservation solutions. There was very little recovery in the control groups, whereas systolic function was preserved in the preconditioned hearts.
Our data showed that preconditioning prevents myocardial stunning in an experimental model of cardiac transplantation when the heart is subjected to 2 hours of ischemia. Longer ischemia times might be more relevant to the clinical situation because increased tolerance to ischemia would extend safe transport time and increase the donor pool. However, there was no indication of systolic dysfunction after transplantation, and in a limited number of observations in our laboratory, this effect was maintained for up to 6 hours. Furthermore, recent reports based on isolated rat heart preparations suggest that preconditioning is effective not only under conditions of hypothermia but that the preconditioning effect might be evident after 12 hours of cold storage. Finally, the application of cardiopulmonary bypass during donor retrieval might not lend itself to clinical cardiac transplantation. Therefore, a different technique of supporting the myocardium during ischemia and reperfusion might have to be designed or the heart might require preconditioning with adenosine, as previously described.
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  J. D. O'Brien and S. E. Howlett Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H768 - H777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ramzy, V. Rao, and R. D. Weisel Clinical applicability of preconditioning and postconditioning: The cardiothoracic surgeons's view Cardiovasc Res, May 1, 2006; 70(2): 174 - 180. [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kloner and S. H. Rezkalla Preconditioning, postconditioning and their application to clinical cardiology Cardiovasc Res, May 1, 2006; 70(2): 297 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A Kloner, M. T Speakman, and K. Przyklenk Ischemic preconditioning: a plea for rationally targeted clinical trials Cardiovasc Res, August 15, 2002; 55(3): 526 - 533. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Farhat, D. Loisance, J.-P. Garnier, and M. Kirsch Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbit Eur. J. Cardiothorac. Surg., March 1, 2001; 19(3): 313 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kevelaitis, A. Oubenaissa, C. Mouas, J. Peynet, and P. Menasche Ischemic preconditioning with opening of mitochondrial adenosine triphosphate-sensitive potassium channels or Na+/H+ exchange inhibition: Which is the best protective strategy for heart transplants? J. Thorac. Cardiovasc. Surg., January 1, 2001; 121(1): 0155 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Alsaddique Ischemic Preconditioning: The Endogenous Power: A Review of the Literature Angiology, May 1, 2000; 51(5): 355 - 360. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
