Reduction of oxidative tissue injury and endothelial dysfunction by graduated reperfusion after cardioplegic arrest in isolated rat hearts.

The aim of this study was to investigate whether or not a graduated resumption of the perfusion pressure after cardioplegic ischaemic arrest will reduce the impact of oxygen free radicals on myocardium and the cardiovasculature. Langendorff-perfused rat hearts were subjected to cardioplegia and subsequent 40 min of global ischaemia at 25 degrees C. Reperfusion was carried out either abruptly (AR) or gradually (i.e., perfusion pressure stepwise increased from 40 to 75 mmHg within 30 min -GR). GR resulted in a significant improvement of percentage recovery of left ventricular systolic pressure as compared to AR. A marked increase of thiobarbituric acid reactive substances (TBARS) was detected in the effluent during AR, accompanied by an impaired release of the endothelial vasodilator NO and diminished coronary flow rates compared to the baseline values. GR resulted in a significant reduction of TBARS in the effluent and promoted a better recovery of coronary flow as well as endothelial release of NO during the later phase of reperfusion. It is concluded that graduated reperfusion is beneficial in reducing free radical mediated peroxidative tissue injury and endothelial dysfunction upon reoxygenation.

Synthesis of high energy phosphates during cold ischemic rat liver preservation with gaseous oxygen insufflation.

The depletion of biochemical energy stores during anoxic ischemic preservation is a major problem affecting the viability of the graft in transplantation medicine. After cessation of blood flow and, thus, lack of metabolic substrates and oxygen supply, a swift decrease of energy-rich phosphates can be observed in the tissue, since endergonic metabolic processes continue, but no further oxidative regeneration of biochemical energy stores will take place. We investigated the effect of a continuous gaseous oxygen supply via the venous vessels during extended ischemic preservation of rat livers in University of Wisconsin preservation solution for 48 hr. Results showed that aerobic ischemic storage not only prevented the depletion of biochemical energy stores, but promoted a de novo synthesis of high energy phosphates, and significantly enhanced the functional recovery of the organs after postischemic reperfusion. The findings suggest that maintenance of oxidative energy metabolism largely protects the organ during ischemia and may enable organ viability even after extended preservation times.

Impairment of grafts by short-term warm ischemia in rat liver transplantation.

The mechanism of warm ischemic damage was investigated by assessing hepatic energy metabolism, mitochondrial functions, and lipid peroxidation (LP) of transplanted liver grafts in rats. Donor livers were stored ischemically either for 90 min at 4 degrees C (control) or for 20 min at 37 degrees C and 70 min at 4 degrees C (warm ischemia). In the control group, adenosine 5'-triphosphate (ATP) recovered within 8 min to 86% of the normal preischemic value (10.30, SEM 0.26 mumol/g dw). Total adenine nucleotides (TAN) recovered to 14.83 (SEM 0.22) mumol/g dw within 30 min, as compared with a normal level of 15.44 (SEM 0.36) mumol/g dw. The energy charge potential (ECP) immediately recovered to 0.79 (SEM 0.01) within 8 min (normal, 0.81, SEM 0.01). Mitochondrial phosphorylation rate (PR) was not significantly altered. LP averaged 451 (SEM 10) nmol/g dw in normal livers and did not change even during reperfusion (504, SEM 79, nmol/g dw, at 15 min). In contrast, in the warm ischemic group, ATP recovered only to 65% of the normal value even at 30 min (P less than 0.01), and TAN remained significantly lower than the control value (12.39, SEM 0.47, mumol/g dw, P less than 0.001). PR was normal at the end of warm ischemia, was significantly reduced at the end of the total ischemic period (P less than 0.001 and P less than 0.01, as compared with control and normal values, respectively), and gradually recovered over 30 min. LP increased and reached the maximum of 795 (SEM 84) nmol/g dw at 15-min reperfusion (P less than 0.05). In grafts treated with 50 mg/kg bw allopurinol (i.v.) 10 min prior to the onset of warm ischemia, ATP and ECP recovered to normal values at 30 min, and TAN was significantly higher than in the warm ischemic group (13.28, SEM 0.28, mumol/g dw, P less than 0.05). PR was maintained at normal values, and LP was increased but to a lesser degree than in the ischemic group. It is concluded that the delayed recovery of ATP metabolism in the warm ischemic group might be due to the loss of adenine nucleotides and the decreased PR, and that allopurinol has a protective effect against warm ischemic damage.

Reduction of proteolysis by venous-systemic oxygen persufflation during rat liver preservation and improved functional outcome after transplantation.

An increase of cytosolic proteolytic activity during ischemic preservation and consecutive tissue degradation have recently been recognized as a major pathogenetic factor for liver injury during ischemia/reperfusion. In the present study, we propose a method for preventing proteolytic tissue disintegration, which results in improved recovery of the liver after transplantation. Livers were harvested from rats and stored for 24 hr at 4 degrees C in University of Wisconsin solution (group A). Others were additionally persufflated with gaseous oxygen via the inferior caval vein during this time (group B). At the end of ischemic preservation, proteolysis was confirmed in group A, with significantly elevated tissue levels of free alanine and free amino groups, whereas proteolysis was prevented in group B. After transplantation, the integrity of the graft was significantly improved in group B, in which there was a 50% reduction of plasma activities of alanine amino-transferase and a twofold increase in hepatic bile production after the onset of reperfusion, as compared with group A. Moreover, venous-systemic oxygen persufflation during cold preservation significantly attenuated the rise in plasma levels of malondialdehyde (MDA) after liver transplantation. In conclusion, venous-systemic oxygen persufflation during ischemic storage prevents tissue proteolysis and reduces parenchymal injury after transplantation in vivo; this technique may, thus, represent a useful adjunct in long-term liver preservation with University of Wisconsin solution.

Biophysical aspects of liver aeration by vascular persufflation with gaseous oxygen.

BACKGROUND: Venous systemic oxygen persufflation of the liver (i.e., gaseous insufflation of oxygen via the venous vascular system) has proven to be an effective tool for preventing anoxic tissue injury during extended time periods of ischemic preservation. It also allows for an improved recovery of the persufflated organ after orthotopic transplantation. METHODS: Biophysical aspects of the persufflation technique with regard to persufflation pressure (9 mmHg versus 18 mmHg) and oxygen concentration (pure oxygen versus air) in the persufflation gas were investigated in rat livers, using epi-illumination microscopic detection of autofluorescence of NADH, which accumulates in anoxic tissue. RESULTS: We demonstrated that a low-pressure persufflation (9 mmHg) is as sufficient as a higher pressure persufflation (18 mmHg) in oxygenating the ischemic organ. Moreover, oxygenation of the liver was found to be complete and rather homogeneous upon the pure oxygen persufflation, irrespective of the insufflation pressure used. In contrast, insufflation of air instead of pure oxygen resulted in insufficient aeration of the liver, even at the higher persufflation pressure of 18 mmHg. CONCLUSIONS: Our results indicate that the oxygen concentration of the persufflation gas rather than the persufflation pressure is a determinant of successful tissue oxygenation during cold storage.

A simple method for orthotopic liver transplantation in the rat. Cuff technique for three vascular anastomoses.

A simple method for orthotopic liver transplantation in the rat is described in detail. A cuff technique was applied to all anastomoses of the supra- and infrahepatic venae cavae and the portal vein. It simplified and shortened the implantation of the graft as well as eliminating the need for microvascular suture technique. In the last series of 20 transplants, the survival rate was 85% after 1 week and 55% after 2 months with normal hepatocellular function.

Successful transplantation of porcine livers after warm ischemic insult in situ and cold preservation including postconditioning with gaseous oxygen.

BACKGROUND: In order to reduce the shortage of viable donor livers for organ transplantation, a method has been developed that allows even predamaged livers from nonheartbeating donors to be used as transplantable organs. METHODS: Porcine livers were harvested 45 min after cardiac arrest of the nonheparinized donor, preflushed with heparinized saline solution, and subsequently rinsed with University of Wisconsin solution, to which superoxide dismutase was added as an oxygen free radical scavenger. Thereafter, the livers were persufflated with gaseous oxygen via the venous vascular system while immersed in University of Wisconsin solution at 4 degrees C for 4 to 5 hr. RESULTS: After orthotopic transplantation, all of the livers conditioned with gaseous oxygen were able to support life-sustaining function during the whole observation period of 7 days post transplantation, while no survival of the recipients could be obtained without the described treatment. CONCLUSIONS: The present study establishes a new perspective for the use of ischemically altered livers from nonheartbeating donors for organ transplantation under clinical circumstances.

Hypothermic storage alone in lung preservation for transplantation: a metabolic, light microscopic, and functional analysis after 18 hours of preservation.

BACKGROUND: Current lung preservation consists of flushing of the donor organs, with successive hypothermic storage in an inflated state. Recently, hypothermic storage alone was reported to be superior in terms of functional recovery. This study was designed to investigate the metabolic, morphologic, and functional consequences of hypothermic storage alone, in experimental lung preservation. METHODS: Orthotopic left-sided lung transplantation was performed in pigs. Donor lungs were flushed with Euro-Collins solution (n=6) or simply explanted (n=6) and stored for 18 hr at 4 degrees C. After this, left-sided single lung transplantation was performed. Sham-operated animals (n=6) served as control. Morphology and metabolism were analyzed in normal lungs, after ischemia and at the end of reperfusion. Gas exchange and pulmonary hemodynamics of the transplanted organs were measured, after exclusion of the native lung from perfusion and ventilation. RESULTS: Metabolic and morphologic evaluation did not show a significant difference between the groups at the end of ischemia. Lungs preserved by hypothermia alone showed a functional recovery close to sham-operated animals and superior to flushed organs. CONCLUSIONS: Hypothermia alone is a sufficient means of preservation for explanted lungs for at least 18 hr.

No evidence for a protective effect of ascorbic acid on free radical generation and liver injury after hemorrhagic shock in rats.

Oxygen free radicals have been shown to be implicated in ischemic tissue injury, and free radical-induced reactions may also play an important role in the pathophysiology of circulatory shock. The present study was designed to investigate the potential use of ascorbic acid as an exogenous antioxidant on the liver's recovery from hemorrhagic shock in situ. Rats (fasted overnight) were subjected to 60 min of hemorrhagic shock (HS) (mean arterial pressure = 40 mmHg) under pentobarbital anesthesia, followed by retransfusion of the shed blood. One-half of the animals (n = 6) were injected with 10 mg/kg of ascorbic acid prior to induction of shock, while untreated animals (n = 6) received the same volume of saline solution. in untreated animals, systemic plasma levels of malondialdehyde rose from 1.07 +/- .08 during normotension (NT) to 1.36 +/- .18* 60 min after resuscitation (RS), documenting oxygen free radical-induced lipid peroxidation. Accordingly, plasma levels of alanine aminotransferase (16.5 +/- 2.5; 34.9 +/- 12.3*; 105.8 +/- 68.7* U/L; NT/HS/RS) and ammonia (127 +/- 40; 532 +/- 160*; 304 +/- 244* micrograms/dL) rose significantly during the experiment. Hepatic ATP content of the liver fell from 4.8 +/- .83 to .56 +/- .27* after HS and recovered partially to 2.7 +/- 1.6* mumol/g after RS. Leukocyte infiltration in the liver, indicated by tissue levels of myeloperoxidase, remained constant during HS but rose during RS (37.9 +/- 18.5; 38.6 +/- 16.4; 81.4 +/- 30.7*, arbitrary units), thus documenting an inflammatory reaction after HS. In the ascorbic acid group, plasma levels of malondialdehyde were comparable to those of untreated animals after RS, as were enzyme concentrations and ammonia. No differences were observed with regard to the tissue concentrations of ATP or myeloperoxidase. Mean arterial blood pressure as well as liver tissue perfusion, as measured by Laser Doppler flowmetry, did not show significant differences between the groups. It was concluded that, although an effect of oxygen free radicals on liver tissue could be found during and after HS, treatment with ascorbic acid alone, in our model, failed to ameliorate the recovery of the animals upon resuscitation (values are mean +/- SD; *, p < .05 vs. NT; one-way ANOVA).

Protective effect of heat shock pretreatment with heat shock protein induction before hepatic warm ischemic injury caused by Pringle's maneuver.

BACKGROUND: Induction of heat shock proteins is thought to have a > cytoprotective effect against environmental stress and to result in a better ischemic tolerance. The protective ability of heat exposure and heat shock protein 72 (HSP 72) induction before warm ischemia caused by Pringle's maneuver was evaluated in rats. METHODS: Heat exposed rats (HS) were compared with control animals (C). The gene expression (messenger RNA) of HSP 72 and HSP 72 were detected by Northern and Western blot analyses. During 40 minutes of in situ reperfusion, liver energy metabolism and levels of standard liver enzymes were evaluated. The survival rate was determined after postoperative day 7. RESULTS: After heat exposure and recovery, messenger RNA of HSP 72 and HSP 72 can be detected strongly in HS group but not in C group. During reperfusion HS group exhibited a significantly (p < 0.01) improved energy metabolism, and the release of liver enzymes was significantly (p < 0.001) reduced compared with C group. Seven-day survival rate was 100% in HS group but at 50% was significantly impaired (p < 0.05) in C group. CONCLUSIONS: Heat exposure associated with HSP induction has a significant protective effect against warm ischemic liver injury, which results in a relevant improvement of survival rate.

Effect of glutamine or glucagon-insulin enriched total parenteral nutrition on liver and gut in 70% hepatectomized rats with colon stenosis.

BACKGROUND: Malnutrition of enterocytes is believed to facilitate the breakdown of the intestinal mucosal barrier, furthering a translocation of enteric bacteria with subsequent severe infection, which has been described after extensive hepatectomy. Glutamine and glucagon insulin are said to attenuate the malnutrition of enterocytes. To determine whether this was true, the effects on the remnant liver and the gut of total parenteral nutrition supplemented by admixtures of glutamine and/or glucagon insulin were investigated in rats subjected to massive hepatectomy and transient intestinal stasis. STUDY DESIGN: Rats underwent a permanent cannulation of the superior caval vein without restraining their mobility, a 70% hepatectomy, and a 24 hour string-ligation stenosis of the colon. A standard total parenteral nutrition solution was infused without or with 2% glutamine and without or with glucagon-insulin supplementation, respectively. RESULTS: Glutamine and glucagon-insulin supplemented total parenteral nutrition increased ileal mucosal DNA concentrations during and after intestinal stasis. Glutamine or glucagon-insulin alone had less pronounced effects. In the liver, the combined supplementation resulted in reduced adenosine triphosphate concentrations and increased mitochondrial adenosine triphosphate synthesis as well as in an early increase in DNA concentrations. CONCLUSION: Glutamine and glucagon-insulin enriched total parenteral nutrition attenuates malnutrition of enterocytes after massive abdominal stress and promotes liver regeneration after extensive hepatectomy.

Parenchymal and vascular endothelial cell injury in the hypoxic and reperfused rat liver. Evidence for superoxide anion generation by perfusion with ferricytochrome c.

Isolated perfused livers from rats fasted overnight were subjected to 90 min of low-flow hypoxia followed by reoxygenation for 30 min. Intra-hepatic generation of superoxide anion was analysed by continuous perfusion with 40 mumol/l of oxidized cytochrome c, the reduction of which was measured spectrophotometrically in the effluate. Reduction of cytochrome c as an indicator for hepatic superoxide anion generation remained constant during pre-hypoxic perfusion and during hypoxia. Upon reperfusion, an initial peak was observed to 47.2 +/- 3.8 nmol/g/min followed by a stable plateau above pre-hypoxic values. Both peak and plateau were significantly attenuated in the presence of 80,000 U/l superoxide dismutase (SOD). Accordingly, tissue contents of lipid peroxides were significantly lower at the end of reperfusion (976 +/- 73 vs 1153 +/- 71 nmol/g*), enzyme leakage [U/g/min] from the endothelium (PNP: 8.4 +/- 4.2 vs 17.2 +/- 3.4**) and from the hepatic parenchyma (Alt: 108 +/- 35 vs 170 +/- 23*) was significantly reduced during reperfusion and oxygen consumption was elevated in the presence of SOD (3.27 +/- 0.34 vs 2.71 +/- 0.37*). It is concluded that reactive oxygen species arise in the vascular lumen or the space of Disse after prolonged hypoxia of the liver, altering the functional outcome of the organ upon reoxygenation. SOD is able to protect against these alterations. * P < 0.05; ** P < 0.01.

Miniaturized heart-lung machine.

The miniaturized heart-lung machine consists of commercially available roller pumps, a flexible heat exchanger, a newly devised bubble oxygenator, and polyethylene cannulas and silicone tubes. The minimum and maximal priming volume of the entire system is 4.7 and 16.7 mL, respectively. The efficiency of the system is reflected in an heat transfer coefficient ranging from 0.96 to 0.31 at flow rates between 1 and 20 mL/min, a high value of oxygen uptake in the range of 0.061 mL O2/min mL blood-1, and low blood trauma with plasma hemoglobin concentrations of 47.5 +/- 5.0 mg/dL after 60 min of in vitro perfusion. The system is a simple, reliable, and efficient miniaturized heart-lung machine for use in small animals.

No beneficial effects of taurine application on oxygen free radical production after hemorrhagic shock in rats.

Oxygen free radical generation contributes to the reinfusion damage after hemorrhagic shock. Taurine has been proposed to have radical scavenging properties under certain experimental conditions. Therefore the present study was undertaken to investigate if taurine would be able to attenuate adverse effects of shock/resuscitation in male rats (fasted over night). Under pentobarbital anesthesia, hemorrhagic shock (HS) was induced for 1 h by bleeding of the animal [mean arterial blood pressure (MAP) = 40 mm Hg] followed by shed blood reinfusion and another 1 h period of resuscitation. Rats were divided into two groups: Treated rats (n = 6) were injected with taurine (40 mg/kg body mass) prior to withdrawal of shed blood; untreated rats (n = 9) received respective volumes of a normal saline solution. In untreated animals, free radical induced lipid peroxidation was documented by an increase of malondialdehyde (MDA) in the systemic circulation (nmol/ml; HPLC measurement) from 1.06 +/- 0.08 during normotension (NT) to 1.35+/- 0.18** 1 h after resuscitation (RS). Accordingly, plasma levels of alanine aminotransferase (ALT) (11 +/- 2; 35 +/- 12; 94 +/- 44 U/l, NT; HS; RS) and ammonia (120 +/- 39; 532 +/- 161; 224 +/- 101 micrograms/dl) changed significantly during the experimental protocol. Hepatic ATPase-content as an indicator of energetic status of the liver fell from 4.8 +/- 0.83 to 0.56 +/- 0.27 after HS and recovered to only 2.7 +/- 1.6 mumol/g after RS. Leukocyte infiltration of the liver was followed by tissue levels of myeloperoxidase (MPO) which did not change during HS, but rose during RS (37.9 +/- 18.5; 38.6 +/- 16.4; 77.5 +/- 24; arbitrary units), documenting an inflammatory reaction after HS. Taurine treated rats showed levels of MDA not different from untreated rats after RS; also no differences were observed concerning enzyme concentrations and ammonia levels. The liver tissue levels of ATP and MPO revealed no differences between the two groups during the various periods of the experiment. Liver tissue perfusion, as measured by Laser Doppler flowmetry, also did not show significant differences between both groups. MAP was significantly higher in the taurine-treated rats during the first 40 min of resuscitation. It is concluded that even a relatively high dose of taurine failed to attenuate the impact of oxygen free radicals and did not improve the recovery of the rats during the early resuscitation period.

Taurine reduces experimental liver injury after cold ischemic preservation and a period of rewarming prior to reperfusion.

Livers of male Wistar rats (250-300 g) were isolated and flushed with 10 ml of Ringer's solution and 10 ml of UW preservation solution. Then the organs were stored for 24 h at 4 degrees C in UW solution. Livers of Group 1 were rinsed with 10 ml of Ringer's solution and reperfused after hypothermic storage with oxygenated Krebs-Henseleit solution (95% O2; 5% CO2) in a nonrecirculating system at constant pressure (10 mmHg) and 37 degrees C. Livers of Group 2 were incubated for 30 min at 37 degrees C prior to reperfusion, in order to simulate rewarming of the organ upon surgical implantation. Livers of Group 3 were treated like Group 2, but taurine was admixed to the UW solution (1 mM). Livers of Group 1 showed little signs of a preservation/reperfusion injury, with low enzyme activities of the parenchymal ALT and endothelial purine nucleoside phosphorylase (PNP) in the postischemic rinse solution (ALT: 19.9 +/- 12.4; PNP: 3.3 +/- 0.4 U/liter), adequate portal flow values about 3 ml/g/min and high O2 uptake at the end of the experiment (VO2: 3.2 +/- 0.4 ml/100g/min). Livers of Group 2 exhibited nearly tenfold higher enzyme activities in the rinse solution (ALT: 247.0 +/- 94.7*; PNP: 29.5 +/- 17.0* U/l) and disturbed tissue perfusion with significantly reduced flow values of about 2 ml/g/min during the first 10 min of reperfusion. As a result, the recovery of O2 uptake was only 2.2 +/- 0.3 ml/100 g/min*. Addition of taurine (Group 3) resulted in a significant reduction of the enzyme loss (ALT: 96.2 +/- 50.0#; PNP:12.4 +/- 7.0# U/liter) and improved portal flow values and O2 uptake at the end of reperfusion (2.7 +/- 0.3 ml/100 g/min#). The results give evidence for the importance of the rewarming period after hypothermic storage, which is inevitable during implantation of the organ in vivo. Taurine seems to exert a protective effect, affecting both the vascular endothelium and parenchymal tissue (*p < 0.05 vs Group 1; # p < 0.05 vs Group 2).

Long-lasting hypoxic preservation of porcine kidney cells. Beneficial effect of taurine on viability and metabolism in a simplified transplantation model.

Taurine administered during hypoxia reduced the cell damage due to O2 deficiency markedly. The beneficial effect outlasted the period of reoxygenation. The mechanisms for the improved survival rates are postulated in a reduced osmoregulatory disturbance of cellular integrity, improved Ca2+ homeostasis and induction of accelerated cellular growth processes. We conclude that taurine supplementation of the conventionally used kidney preservation solution (UW) improves this "gold standard" kidney preservation solution markedly.

Protective effect of taurine on hypoxia and reoxygenation-induced damage of human colon cells (HT 29).

In this experimental model, taurine administered during hypoxia markedly reduced the cell damage due to O2 deficiency, and the beneficial effect outlasted the period of reoxygenation. The mechanisms for the improved survival rates are postulated to be a reduced osmoregulatory disturbance of cellular integrity, improved Ca2+ homeostasis and induction of accelerated cellular growth processes. In our simplified cell culture model the UW solution seems to be the most appropriate solution for the cold (hypoxic) preservation of human colon cells. We conclude, that within this experimental model and under these experimental conditions, taurine supplementation of the conventionally used preservation solutions improved the solutions markedly. Considering our previous studies, taurine seems to be a potent endogenous protective agent against cellular deterioration due to hypoxia and reoxygenation.

Protecting effect of taurine against hypoxic cell damage in renal tubular cells cultured in different transplant preservation solutions.

We conclude that, within this experimental model and under these experimental conditions, taurine supplementation of standard kidney preservation solutions improves survival of kidney cells during hypoxic preservation. The protective effect depends on the taurine concentration, the hypoxic preservation time and the used preservation solution. Physiological taurine concentrations are effective during short hypoxic periods, whereas pharmacological taurine concentrations seem to be needed for longer periods of hypoxia. Within this experimental model University of Wisconsin solution seems to be more effective than Euro collins solution.

Pressure-controlled reperfusion improves postischemic recovery of LV-hypertrophied rat hearts.

The influence of pressure-controlled postischemic reperfusion (Rp) on functional and metabolic parameters in hearts of sham-operated rats and hypertrophied hearts of rats with aortic constriction were studied. Hypertrophied hearts are considered to be more susceptible to ischemia. The hearts were perfused in the Langendorff-technique for thirty minutes at 35 degrees C with Krebs-Henseleit bicarbonate buffer at a perfusion pressure (PP) of 75 mmHg and for five minutes at 15 degrees C with St. Thomas' Hospital cardioplegic solution at a PP of 60 mmHg. After a period of global ischemia of forty minutes' duration at 15 degrees C, reperfusion was started either abruptly (aRp: PP 75 mmHg immediately) or gently (gRp: PP 75 mmHg within thirty minutes); it lasted for forty-five minutes. Intraventricular peak systolic pressure (ISP) was monitored and energy-rich compounds (ATP, ADP, AMP, CrP, free Cr) were analyzed. In normal hearts, metabolic recovery was not affected by the mode of reperfusion, but functional recovery (ISP) averaged 88% of the preischemic control value after gRp as compared with 73% after aRp. In hypertrophied hearts, gentle reperfusion ameliorated both metabolic and functional recovery. At forty-five minute recovery, CrP averaged 5.1 mumol/g ww after aRp and 6.6 mumol/g ww after gRp (p less than 0.01), and ISP amounted to 73% of the preischemic control after aRp and to 85% after gRp.

[Recovery of healthy and hypertrophic hearts after global ischemia and graduated reperfusion]. / Récupération des coeurs sains et hypertrophiés après ischémie globale et reperfusion graduée.

The influence of pressure controlled reperfusion on the postischemic outcome of normal and normotensive hypertrophied rat hearts should be investigated. To induce normotensive cardiac hypertrophy, male Wistar rats received injections of isoprenaline (5 mg/kg s.c. bid for three days). Hearts were excised and perfused according to the Langendorff-technique at a perfusion pressure of 75 mm Hg for 30 min. After cardioplegia and 40 min of global ischemia at 25 degrees C the hearts were reperfuse for 45 min. Reperfusion pressure was increased either abruptly (75 mm Hg immediately) or gradually (from 40 mm Hg to 75 mm Hg within 30 min). Post-ischemic recovery was significantly affected by the mode of reperfusion in normal hearts, in which pressure controlled (gradual) reperfusion was superior to the abrupt reperfusion mode. In hypertrophied hearts, the post-ischemic outcome did not differ from normal hearts when abrupt reperfusion was used, but gradual reperfusion only led to a comparably small improvement of the post-ischemic status.