Ischemic pre-conditioning of 5 minutes but not of 10 minutes improves lung function after warm ischemia in a canine model.

BACKGROUND: Protection from reperfusion injury by ischemic pre-conditioning (IPC) before prolonged ischemia has been proven for the heart and the liver. We now assess the efficacy of IPC to protect lungs from reperfusion injury. METHODS: Eighteen foxhounds (25 to 30 kg) were anesthetized, intubated, and ventilated with a fraction of inspired oxygen of 0.3 at a volume-controlled mode to maintain arterial pCO2 of 30 to 40 mm Hg. After left thoracotomy, we performed warm ischemia for 3 hours by clamping the left hilus, and followed with 8 hours of reperfusion (control, n = 6). In the treated groups, IPC was performed either for 5 minutes followed by 15-minute reperfusion (n = 6, IPC-5), or by 2 successive cycles of 10-minute ischemia, followed by 10-minute reperfusion (n = 6, IPC-10) before prior to the 3-hours warm-ischemia period. Pulmonary compliance and gas exchange were determined separately for each lung, and we recorded pulmonary and systemic hemodynamics. We performed bronchoalveolar lavage (BAL) at the end of the experiment and determined total protein concentration as well as tumor necrosis factor alpha (TNF-alpha) mRNA expression in cell-free supernatant and in BAL cells, respectively. We also assessed the wet/dry ratio of the lung. RESULTS: In the controls, on reperfusion, we encountered a progressive deterioration of gas exchange, especially of the reperfused left lung, which we could largely avoid using the IPC-5 protocol. Similarly, pulmonary compliance steadily declined but was much better in the ICP-5 group. Parallel to the improvement of gas exchange and lung mechanics, we found less total alveolar protein content and TNF-alpha mRNA expression in BAL cells in the IPC-5 than in the controls. However, we did not find IPC-10 to be paralleled by a significant improvement of lung function. Neither IPC-5 nor IPC-10 influenced the pulmonary vascular resistance index or the fluid accumulation in the lung. CONCLUSION: The major finding of the present study was that 5 minutes of IPC improved lung function after 3 hours of warm ischemia of the lung.

Calcitonin gene-related peptide-induced preconditioning improves preservation with cardioplegia.

BACKGROUND: Our recent work has shown that calcitonin gene-related peptide (CGRP) may play an important role in mediation of ischemic preconditioning. Therefore, we tested the hypothesis that CGRP-induced preconditioning protects against myocardial damage after prolonged cardioplegic arrest in isolated rat hearts. METHODS: Six groups were studied: the control, ischemic preconditioning, and CGRP-pretreated groups for both 4- and 8-hour hypothermic ischemia. All hearts were arrested using St. Thomas Hospital cardioplegia, and then reperfused with normothermic Krebs-Henseleit solution for 60 minutes after the 4- or 8-hour hypothermic ischemic period. Hearts were subjected to two cycles of 5-minute ischemia and 10-minute reperfusion in the ischemic preconditioning group. In the CGRP-pretreated group, Krebs-Henseleit solution containing CGRP (5 x 10(-9) mol/L) was substituted for the ischemic period. RESULTS: At 30 minutes of reperfusion after 4-hour storage, left ventricular pressure (mm Hg) and its first derivative (dp/dtmax, mm Hg/s) in the control, ischemic preconditioning, and CGRP groups were 65.2 +/- 5.93 and 1,170 +/- 119, 94.13 +/- 4.93 and 1,825 +/- 145.83, and 85.47 +/- 4.17 and 1,900 +/- 123.13, respectively (p < 0.01). After 8-hour storage, left ventricular pressure (mm Hg) and dp/dtmax (mm Hg/s) in the same groups were 51.07 +/- 5.83 and 815 +/- 107.17, 83.47 +/- 6.54 and 1,480 +/- 120.91, and 84.8 +/- 8.49 and 1,396 +/- 126.16 (p < 0.01). Ischemic preconditioning and CGRP-induced preconditioning also significantly reduced the release of myocardial enzymes. CONCLUSIONS: The present studies suggest that ischemic preconditioning protects against ischemia-reperfusion injury even after 8 hours of hypothermic preservation in isolated rat hearts, and that CGRP exerts preconditioning-like cardioprotection.

Preconditioning improves myocardial preservation in patients undergoing open heart operations.

BACKGROUND: Our previous work has shown that preconditioning can promote the recovery of cardiac function in patients having an open heart procedure. Because preconditioning is regarded as the most powerful form of endogenous myocardial protection, we tested the hypothesis that preconditioning protects against myocardial ischemia-reperfusion injury in patients undergoing prolonged cold crystalloid cardioplegic arrest. METHODS: Thirty patients who had rheumatic heart disease and required both aortic and mitral valve replacement were studied. Patients were randomly divided into two equal groups. Preconditioning was accomplished using two cycles of 2-minute occlusion of the vena cava and aorta followed by 3 minutes of reperfusion under cardiopulmonary bypass. All hearts were arrested with 4 degrees C St. Thomas' Hospital cardioplegic solution. Myocardial protective effects were assessed by changes in myocardial levels of adenosine triphosphate, electrocardiographic activity, leakage of myocardial enzymes, and myocardial contractility. RESULTS: The adenosine triphosphate content in ischemic myocardium was higher in the preconditioning group than in the control group (p < 0.05 90 minutes after ischemia), and there was a significant reduction in release of the myocardial-specific isoenzyme of creatine kinase in the preconditioning group. Preconditioning improved the recovery of myocardial contractility (first derivative of left ventricular developed pressure, 1,490 +/- 102 mm Hg/s versus 1,250 +/- 97 mm Hg/s 30 minutes after reperfusion; p < 0.05), and there was also a protective effect on electrocardiographic activity. CONCLUSIONS: Our results suggest that ischemic preconditioning protects the myocardium in humans from the severe ischemia-reperfusion injury produced after prolonged arrest with cold crystalloid cardioplegia.

Age factor in post-nephrectomy compensatory renal growth.

In a retrospective investigation we found that the endogenous creatinine clearance (Ccr) of 35 nephrectomized patients was lower than that of normal people of comparable age with two intact kidneys. The Ccr level in the post-nephrectomy patients appeared to correlate with the age of the patients at the time of nephrectomy. The average Ccr value was 99.2 ml/min in the younger group, and 54.9 ml/min in the older group. Furthermore, we also found that the measurement of the remaining kidney in the younger group was larger than that of the matched control group, but no difference was found between the measurement of the remaining kidney in the older group and that of the matched control group. Therefore, we suggest that the remaining kidney in patients over 50 years of age may be described as "a low compensatory kidney". The results from an experimental study of Wistar rats indicated that the dry and wet weights of the remaining kidneys of the younger rats which had undergone neptrectomy were 1.53 X 10(-3) g/gwt, and 5.89 X 10(-3) g/gwt respectively, vs 1.05 X 10 g/gwt and 3.82 X 10(-3) g/gwt in older ones. In tissue culture using serum of younger nephrectomized rats, the amount of 3H-TdR incorporation into the monolayer cells of renal cortex was 1,405.4 CPM, whereas it was 1,025.4 CPM by using serum of older nephrectomized rats. In addition, the cells of renal cortices from both younger and older rats had a similar response to the same serum from nephrectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Preconditioning enhances myocardial protection in patients undergoing open heart surgery.

To date, ischemic preconditioning is regarded as the most powerful form of endogenous myocardial protection. For the purpose of surgical myocardial protection, a few clinical studies have investigated the effects of ischemic preconditioning in conjunction with hypothermia or blood cardioplegia during open heart surgery, but the results were controversial. We now tested the hypothesis that preconditioning improves myocardial protection in patients undergoing cold crystalloid cardioplegic arrest. 36 patients needing mitral prosthetic valve replacement for rheumatic heart disease were studied. Patients were evenly divided into two groups at random. Preconditioning was elicited by two cycles of 3 minutes ischemia by occlusion of vena cava and aortic cross-clamping followed by 2 minutes reperfusion under cardiopulmonary bypass. All hearts were arrested using 4 degrees C St. Thomas' Hospital solution before the intracardiac operative program. Myocardial protective effects were mainly assessed by electrocardiac activities, leakage of myocardial enzymes, myocardial contractility, and early postoperative recovery. The results indicated that there was a significant reduction of ST-segment shifting (ST-segment elevation, 0.07 +/- 0.02 vs 0.22 +/- 0.07 mV, p < 0.05, at 4 hours post reperfusion) and smaller release of creatine kinase-MB (87 +/- 11.5 vs 143 +/- 17.2 IU/L, p < 0.05, at 12 hours post reperfusion) in the preconditioning group. Preconditioning also enhanced myocardial contractility (dp/dtmax = 1490 +/- 75 vs 1280 +/- 88 mmHg/sec, at 30 minutes post reperfusion, p < 0.05) and promoted early postoperative recovery. The present study suggests that ischemic preconditioning reduces ischemia-reperfusion injury in human hearts even when combined with cold crystalloid cardioplegia.