Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An isolated rabbit heart preparation was used to characterize the effects of hypothermia on the deterioration in mitochondrial respiratory function and on the calcium overload that occurs during ischemia and reperfusion. Hearts were perfused aerobically with an asanguineous solution for 120 minutes or made totally ischemic for 90 minutes at 37 degrees, 34 degrees, 28 degrees, 22 degrees C, respectively, and reperfused for 30 minutes at 37 degrees C. Mitochondrial function was assessed by measuring calcium content, yield, oxygen consumption, and adenosine triphosphate-producing capacities. In addition, the mechanical function of the hearts was measured together with tissue adenosine triphosphate, creatine phosphate, and calcium content. In a separate series of experiments, the effect of temperature on the initial rate of respiration-supported calcium accumulation of mitochondria from freshly excised, nonperfused rabbit hearts was determined. The hearts made ischemic at 37 degrees C were severely depleted of tissue adenosine triphosphate and creatine phosphate. Their mitochondria accumulated calcium and the oxidative phosphorylating activity was impaired. During reperfusion, tissue and mitochondrial calcium levels were substantially increased, state 3 of mitochondrial respiration was further impaired, and the adenosine triphosphate-generating capacities were severely reduced. Diastolic pressure increased and there was no recovery of developed pressure. Isolated mitochondrial function of hearts made ischemic at 28 degrees and 22 degrees C was protected. There was a less marked increase in tissue and mitochondrial calcium, and the initial rate and total production of adenosine triphosphate were maintained. In these hearts there was an almost complete recovery of mechanical performance at reperfusion, whereas the ischemia-induced depletion of tissue adenosine triphosphate and creatine phosphate was not significantly reduced by hypothermia. The hearts made ischemic at 34 degrees C were only partially protected. These data suggest that a decrease in temperature from 37 degrees to 22 degrees C during ischemia did not significantly prevent depletion of adenosine triphosphate at the end of ischemia but reduced tissue and mitochondrial calcium overload, maintaining mitochondrial function. Thus in our experiments the protective effect of hypothermia might be related to a direct reduction of tissue and mitochondrial calcium accumulation rather than to a slowing in rates of energy utilization. This possibility is supported by the finding that in freshly excised, nonperfused rabbit hearts, hypothermia significantly reduced the initial rate of mitochondrial calcium transport.
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PMID:Effects of temperature on myocardial calcium homeostasis and mitochondrial function during ischemia and reperfusion. 232 31

13C and 31P nuclear magnetic resonance (NMR) spectra were used to assess substrate oxidation and high-energy phosphates in postischemic (PI) isolated rabbit hearts. Phosphocreatine (PCr) increased in nonischemic controls on switching from glucose perfusion to either 2.5 mM [3-13C]pyruvate (120%, n = 7) or [2-13C]acetate (114%, n = 8, P less than 0.05). ATP content, oxygen consumption (MVO2), and hemodynamics (dP/dt) were not affected by substrate availability in control or PI hearts. dP/dt was 40-60% lower in PI hearts during reperfusion after 10 min ischemia. Hearts reperfused with either pyruvate (n = 11) or acetate (n = 8) regained preischemic PCr levels within 45 s. Steady-state ATP levels were 55-70% of preischemia with pyruvate and 52-60% with acetate. Percent maximum [4-13C]glutamate signal showed reduced conversion of pyruvate to glutamate via the tricarboxylic acid (TCA) cycle at 4-min reperfusion (PI = 24 +/- 4%, means +/- SE; Control = 48 +/- 4%). The increase in 13C signal from the C-4 position of glutamate was similar to control hearts within 10.5 min. The increase in [4-13C]glutamate signal from acetate was not different between PI and control hearts. The ratio of [2-13C]Glu:[4-13C]Glu, reflecting TCA cycle activity, was reduced in PI hearts with acetate for at least 10 min (Control = 0.76 +/- 0.03; PI = 0.51 +/- 0.09) until steady state was reached. Despite rapid recovery of oxidative phosphorylation, contractility remained impaired and substrate oxidation was significantly slowed in postischemic hearts.
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PMID:Reduced substrate oxidation in postischemic myocardium: 13C and 31P NMR analyses. 233 71

Hearts from 110 consecutive adult autopsies were examined to determine the frequency and predisposing clinical and pathologic features of acute left ventricular papillary muscle ischemia. Acute infarcts of papillary muscles were present in 23% of the hearts and were more frequent than acute infarcts of their corresponding ventricular walls. Patients with acutely infarcted papillary muscles were more likely to have significant stenosis of the corresponding coronary artery than were patients with normal papillary muscles. Increasing heart weight was also associated with increased frequency of papillary muscle acute infarction. Patients with acutely infarcted papillary muscles were more likely to have had hypertension and to have suffered significant hypotension prior to death than were patients with normal papillary muscles.
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PMID:Clinical and pathologic factors contributing to acute papillary muscle ischemia. 234 64

Hearts isolated from rats treated 36 hr before with interleukin 1 (IL-1) had increased glucose-6-phosphate dehydrogenase (G6PD) activity and decreased hydrogen peroxide levels and injury after global ischemia (I, 20 min)/reperfusion (R, 40 min) compared with hearts from untreated rats. Hearts isolated from rats treated 6 hr earlier with IL-1 also had increased polymorphonuclear leukocytes (PMN), H2O2 levels, and oxidized glutathione (GSSG) contents compared with hearts from untreated rats. Depletion of circulating blood PMN by prior treatment with vinblastine prevented both early (from treatment 6 hr before study) IL-1-induced increases in myocardial PMN accumulation, H2O2 levels, and GSSG contents and late (from treatment 36 hr before study) increases in myocardial G6PD activity and protection against I/R. Our results indicate that IL-1 pretreatment causes an early (6 hr after IL-1 treatment) myocardial PMN accumulation and most likely an H2O2-dependent oxidative stress, which contributes to late (36 hr after IL-1 treatment) increases in myocardial G6PD activity and decreases in I/R injury.
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PMID:Interleukin 1 pretreatment decreases ischemia/reperfusion injury. 236 21

Hyperthermia induces the synthesis of the 71-kDa heat-shock protein (heat-shock response) in all rat tissues, including heart. We examined whether induction of the heat-shock response alters the response of isolated hearts to ischemia and reperfusion. Anesthetized male rats were pretreated with 15 min of hyperthermia (42 degrees C) and then recovered for 0, 24, 48, 96, or 192 h. Hearts were isolated from control and hyperthermia-treated rats and retrogradely perfused. Greatest recovery occurred in 48-h postheat-shock hearts; after 30 min of reperfusion there was a 38, 62, and 62% recovery of force, +dF/dt, and -dF/dt, respectively, and 17, 36, and 30% recovery, respectively, for the control hearts. Creatine kinase efflux during reperfusion was reduced by 75% for 24-h postheat-shock hearts. The antioxidative enzyme catalase was increased 24, 48, and 96 h posthyperthermia. Treatment of rats with 3-amino-1,2,4-triazole (1 g/kg body wt), which irreversibly inactivates catalase, 30 min before isolation of hearts, abolished the hyperthermia-induced enhancement of postischemic recovery. These results show a strong relationship between the acquisition and decay of the enhanced postischemic ventricular recovery and the hyperthermic induction of the heat-shock response indicated by the accumulation of heat-shock protein HSP71 (mol mass 71 kDa) and the increase in catalase activity.
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PMID:Acquisition and decay of heat-shock-enhanced postischemic ventricular recovery. 238 21

The potential benefit of transient hypothermic reperfusion of the ischemic myocardium was investigated in isolated working rat hearts (n = 6/group) subjected to 25 min of global ischemia at 37 degrees C. Hearts were reperfused in the Langendorff mode at 5, 10, 20, 30, or 37 degrees C for 10 min plus 5 min at 37 degrees C before assessment of functional recovery (working mode). Compared with normothermic reperfusion (recovery of cardiac output = 42.3 +/- 6.1%), transient hypothermia failed to improve the recovery of cardiac output, which was 47.9 +/- 12.7 (P = NS), 54.3 +/- 11.5 (P = NS), 25.3 +/- 2.7 (P = NS), and 6.4 +/- 3.8% (P less than 0.05) in the 30, 20, 10, and 5 degrees C groups, respectively. Reduced recovery in the 5 degrees C group was reflected in increased creatine kinase leakage from 0.26 +/- 0.04 IU.ml-1.g dry wt-1 (37 degrees C reperfusion) to 0.62 +/- 0.12 IU. ml-1.g dry wt-1 (5 degrees C reperfusion; P less than 0.05). Brief periods (3 x 1 min) of hypothermic (5 degrees C) perfusion during normothermic Langendorff reperfusion (15 min) also reduced recovery of cardiac output to 12.1 +/- 7.2% (P less than 0.01). In additional studies, hearts were subjected to a 2-min preischemic infusion with the St. Thomas' Hospital cardioplegic solution before either 25 or 35 min of normothermic ischemia and reperfusion with transient hypothermia at 5, 10, 20, or 30 degrees C. Once again hypothermic reperfusion failed to improve recovery but detrimental effects were not observed in the 5 degrees C group. These results indicate no beneficial effect of transient hypothermic reperfusion on recovery of function measured following global normothermic ischemia.
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PMID:Transient hypothermic reperfusion and postischemic recovery in isolated rat heart. 239 94

The influence of glucocorticoid supplementation to cardioplegic solutions is still open to debate. The isolated working rat heart model was used to test the efficacy of glucocorticoid (methylprednisolone sodium succinate (MPSS] supplementation to 2 clinical cardioplegic solutions. Hearts were subjected to either 80 minutes or 120 minutes of hypothermic (18.5 degrees C) global ischemia after single-dose administration (4 degrees C) of one of the cardioplegic solutions A ("Hamburg" solution) or B (simple potassium-based solution). Each cardioplegic solution was infused containing either MPSS in the clinically used concentration (250 mg/l or 500 mg/l for solution A and B, respectively) or without MPSS. The recovery of aortic flow, coronary flow, peak aortic pressure and heart rate was compared with preischemic control values. Creatine kinase (CK) release was measured in the early reperfusion period and the myocardial content of ATP was measured at 30 minutes of reperfusion. Solution B provided only a moderate protection against ischemic damage. Inclusion of MPSS 500 mg/l slightly improved the recovery of physiological indices, reduced CK leakage and increased myocardial ATP. Solution A provided a more effective protection against ischemia. The addition of MPSS in this situation did not affect the overall postischemic recovery. We suggest that the addition of MPSS may improve the protective properties of a cardioplegic solution when the ischemic injury is rather severe.
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PMID:Steroids and cardioplegia. An experimental evaluation of glucocorticoid supplementation to cardioplegic solutions in clinical use. 240 26

Uneven distribution of temperature and the persistence of electro-mechanical activity after aortic cross-clamping are 2 factors limiting the myocardial protection during cardioplegic arrest, especially in hypertrophied hearts which are known to be extremely vulnerable to ischemia. In the present study regional myocardial temperature (T) was continuously controlled, and the time until arrest occurred (delta t) was determined in 61 patients undergoing aortic valve replacement. In addition, the myocardial contents of high energy phosphates and lactate were assessed. Three different cardioplegic solutions were employed: In the first group we used Bretschneider solution (Br), in the second group St. Thomas' solution (St), and in the third group the so-called "Hamburg cardioplegia" (H). During cardiac arrest the regional myocardial temperature was adjusted to temperatures not exceeding 15 degrees C by intermittent infusions of cold cardioplegic solution. We found a positive correlation between left ventricular muscle mass (LVMM) and delta t. A negative correlation existed between LVMM and adenosine triphosphate (ATP) contents at the end of the ischemic period. The cooling characteristics and delta t were significantly longer and the cooling to 15 degrees C was less rapid when H was used. Adenosine-triphosphate contents were well preserved during ischemia in all 3 groups. We conclude that all 3 cardioplegic solutions tested protect the hypertrophied myocardium adequately if the regional myocardial temperature does not increase above 15 degrees C during cardiac arrest. Hearts with a higher LVMM showed a decreased myocardial ATP content at the end of the ischemic period. Therefore, the LVMM may limit myocardial protection.
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PMID:Protection of the hypertrophied human heart by adjusting regional myocardial temperature to a safe level. 241 76

Isolated guinea pig hearts were subjected to 40 min of low flow global ischemia followed by 30 min of reperfusion. The effects of prostacyclin (PGI2) (10 pg/ml-10 ng/ml) on the response of hearts to ischemia and reperfusion were studied. Ischemia caused a 55% decline in contractile force and the development of contracture. Sinus bradycardia and varying degrees of atrioventricular conduction block were observed. Reperfusion was associated with rapid recovery of contractile force and a gradual decline in resting tension. PGI2 (1 ng/ml) enhanced ischemic contracture significantly at 10 and 20 min (P less than .05). Hearts made ischemic in the presence of PGI2 developed higher degrees of atrioventricular conduction block when compared to controls. Reperfusion in the presence of 1 or 10 ng/ml of PGI2 caused a significant decline in recovery of force (P less than .05) and enhanced reperfusion-associated contracture. We examined the influence of verapamil (100 ng/ml) and lowering external calcium to 1.25 mM on hearts subjected to ischemia and reperfusion in the absence of presence of PGI2 (1 ng/ml). Neither verapamil nor 1.25 mM calcium exerted significant effects on the decline of contractile force during ischemia or on recovery of contractility upon reperfusion. However, verapamil did reverse the reperfusion-associated cardiodepressant effects of PGI2. Verapamil abolished contracture in control hearts after 5 and 10 min of reperfusion and prevented the enhancement of contracture in hearts reperfused in the presence of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Concentration-dependent effects of prostacyclin on the response of the isolated guinea pig heart to ischemia and reperfusion: possible involvement of the slow inward current. 244 Oct 27

The hypothesis was tested, if the addition of 2-mercaptopropionylglycine (MPG, Thiola) to a crystalloid cardioplegic solution provides superior myocardial protection as assessed by biochemical and morphological parameters. Five mongrel dogs underwent a 60-min hypothermic cardioplegic arrest (untreated group). In six dogs, MPG (1.5 mmol/l) was added to the crystalloid cardioplegic solution (treated group). Thereafter a reperfusion phase of 60 min was established. At the end of the reperfusion phase samples for mitochondrial respiration parameters and for mitochondrial energization were collected. Samples for ultrastructure and negative staining were taken at the end of ischemia, and after 15, 30 and 60 min of reperfusion. Hearts which were treated with the MPG-enriched cardioplegic solution showed a better ultrastructure (1 (1/1) vs 2 (2/2), p less than 0.001) and superior preservation of the mitochondrial ATPases (2.4 +/- 2.0 versus 8.4 +/- 2.7, p less than 0.05) as compared to the untreated group at the end of ischemia. At the end of reperfusion, mitochondrial respiration, and energization of the mitochondria was improved significantly with the addition of MPG as compared to the untreated group.
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PMID:Myocardial protection by 2-mercaptopropionylglycine during global ischemia in dogs. 247 Mar 81


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