Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.
...
PMID:Protective effects of diltiazem and ryanodine against ischemia-reperfusion injury in neonatal rabbit hearts. 832 Oct 5

We investigated changes in myocardial pH during cardioplegic arrest with five methods of preservation at 15 degrees +/- 1 degree C. Twenty-five dogs were subjected to cardiopulmonary bypass for 150 minutes. Group I (control) had hypothermia only. Group II received THAM-buffered blood cardioplegia, group III a bicarbonate-buffered blood cardioplegic solution, group IV infusions of hyperkalemic blood, and group V oxygenated St. Thomas 2 solution. After 120 minutes of ischemia, interstitial pH in group I was markedly depressed (6.4 +/- 0.07; p < 0.01). The pH in groups II and IV was well maintained (7.23 +/- 0.05 and 7.27 +/- 0.07) and differed significantly (p < 0.05) from that of the remaining groups. The pH in groups III and V was less well maintained (7.14 +/- 0.02 and 7.01 +/- 0.05), with no significant difference (p > 0.05) between these two groups. Postreperfusion functional recovery after 45 minutes was 24% +/- 6% in group I, 92% +/- 3% in group II, 82% +/- 5% in group III, 84% +/- 4% in group IV, and 66% +/- 6% in group V. Creatine kinase levels were significantly (p < 0.01) increased and ultrastructural damage was more prominent in group I compared with the remaining groups. Myocardial water content significantly increased in all groups. We conclude that a strongly buffered blood-based cardioplegic solution is more effective in preventing interstitial acidosis during moderate hypothermia and that maintenance of an optimal tissue pH plays an important role in postischemic functional recovery.
...
PMID:Interstitial pH during myocardial preservation: assessment of five methods of myocardial preservation. 843 Oct 54

Cell damage within the sinusoidal lining of human liver grafts during transplantation is an early event that is critical in ischemia-reperfusion injury and probably plays a key role in primary liver dysfunction after transplantation. No simple biochemical marker for sinusoidal injury is currently available. Because creatine kinase activity has been described in heart endothelial cells, we hypothesized that release of this enzyme might serve as an index of sinusoidal injury. To test this hypothesis, we used several in vivo and in vitro experimental models. Occlusion of the rat hepatic pedicle in situ for 60 min (normothermic ischemia) induced a significant increase in serum creatine kinase levels relative to those in laparotomized controls (2,530 +/- 530 vs. 389 +/- 64 IU/L, mean +/- SEM; p < 0.005). In the isolated perfused rat liver, 60-min ischemia induced early (< or = 3 min) creatine kinase and AST release (0.87 +/- 0.14 vs. 0.08 +/- 0.01 IU/min/gm liver, respectively). A similar phenomenon was observed after 24-hr or 48-hr hypothermic conservation in University of Wisconsin solution. Electrophoretic analysis and immunoinhibition studies showed that creatine kinase activity comprised creatine kinase-BB (approximately 50%) and mitochondrial creatine kinase. Trypan blue infusion showed a loss of viability in sinusoidal cells, whereas hepatocytes were relatively spared. Finally, murine sinusoidal cells were isolated, cultured and then lysed by a freeze-thaw cycle and sonication. Creatine kinase activity was found in endothelial cells (creatine kinase-BB), Kupffer cells (creatine kinase-BB) and Ito cells (creatine kinase-MM). Creatine kinase-BB was not found in hepatocytes, but mitochondrial creatine kinase was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Creatine kinase-BB: a marker of liver sinusoidal damage in ischemia-reperfusion. 827 65

Examination was made of cardioprotective effect related to the ATP-sensitive K+ (KATP) channel on isolated globally ischemic reperfused rat hearts using cromakalim, a putative ATP-sensitive K+ channel opener. The hearts were subjected to 20 min Langendorff perfusion with Krebs Henseleit Bicarbonate Buffer (KHBB) (70 cmH2O, 37 degrees C), followed by 30 min ischemia at 36 degrees C, and 30 min reperfusion with KHBB, with (cromakalim group) or without (control group) pretreatment by 10 microM cromakalim added to KHBB for 5 min prior to ischemia. Before ischemia, no significant change in heart rate (HR), left ventricular developed pressure (LVDP) or coronary flow (CF) by 10 microM cromakalim could be detected. The two groups were the same in CF during reperfusion, but recovery of HR and LVDP significantly improved in the cromakalim group. Creatine kinase (CK) leakage in the cromakalim group was significantly less than in the control group during reperfusion. Cromakalim is thus shown to reduce the myocardial injury during ischemia and reperfusion. Intracellular Ca2+ content of the cromakalim group appeared lower than that of the control group at 30 min of reperfusion. At 5-30 min of reperfusion, in the cromakalim group, intracellular Ca2+ storage was prevented, leading to a good recovery of cardiac function, while in the control group, intracellular Ca2+ increased and recovery of cardiac function was poor. After pretreatment with 10 microM cromakalim, intracellular K+ content of the cromakalim group was significantly lower than in the control group before ischemia. At 5 min of reperfusion, intracellular K+ content of the cromakalim group was slightly less than that of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Cardioprotective effect of cromakalim, a K+ channel opener, on isolated globally ischemic and reperfused rat hearts]. 847 73

Creatine kinase (CK) and its brain-specific isoenzyme (CK-BB), neuron-specific enolase (NSE), neural cell adhesion molecule (NCAM) and the ions sodium, potassium, chloride and calcium were measured both in CSF and serum and inorganic phosphate in CSF in order to assess their prognostic value in total brain ischemia due to cardiac arrest. The samples were collected at 4, 28 and 76 h after resuscitation. Twenty consecutive patients resuscitated from ventricular fibrillation or asystole were included in the study. Nine of the patients recovered consciousness (recovered) but eleven remained comatose (disabled). The follow-up period was 2 years after which only one patient was still alive. The earliest statistically significant differences between neurologically recovered and disabled patient groups were seen in CSF inorganic phosphate (P = 0.030) already at 4 h and CK-BB (P = 0.046) and NSE (P = 0.020) activity at 28 h. Later, at 76 h after the resuscitation CSF NSE differentiated the groups most clearly (P = 0.014). The values were higher in the disabled patients. A negative correlation between CSF parameters and Glasgow Coma scores was also seen at these timepoints. Statistically significant differences between the groups were seen in both CSF and blood pCO2, pO2, base excess (BE) and actual bicarbonate (HCO3-). CSF or serum NCAM has no prognostic value in anoxic-ischemic coma. The results suggest that in CSF CK-BB and NSE are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value.
...
PMID:CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man. 850 98

Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 +/- 5 micrograms/gm ventricle versus 117 +/- 4 micrograms/gm ventricle, p < 0.05). Developed pressure at end reperfusion was 62% +/- 2% of equilibration in treatment group versus 37% +/- 2% in control group, p < 0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) vs 1.00 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 +/- 0.07 mm Hg/(microliter O2/min/gm ventricle, p < 0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% +/- 2% for the treatment group vs 33% +/- 3% in the control group, p < 0.005; phosphocreatine 49% +/- 3% in the treatment group vs 35% +/- 3% in the control group, p < 0.005) and reperfusion (adenosine triphosphate 18% +/- 3% in the treatment group vs 11% +/- 2% in the control group, CTRL p < 0.05; phosphocreatine 45% +/- 2% in the treatment group vs 23% +/- 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% +/- 3% of equilibration activity vs 65% +/- 2% in the control group, p < 0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.
...
PMID:Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment. 858 19

The effect of three cardioplegic protocols on perioperative myocardial injury was studied in 62 coronary artery bypass grafting (CABG) patients randomized into three groups with either antegrade or retrograde cold blood cardioplegia, or coronary sinus occlusion during antegrade supply. During the aortic cross-clamp time anterior and posterior septal temperatures were recorded, indicating the distribution of cardioplegic solution within the myocardium. Serum creatine kinase (CK), CK-isoenzyme MB and myoglobin as well as 12-lead electrocardiograms (ECG) were analyzed. Statistical analysis showed no effect of the cardioplegic protocol, whereas the patient's preoperative status, aortic cross-clamp time and intraoperative myocardial temperature had significant (P < 0.05) effects on immediate postoperative CK and CK-MB enzyme release. Creatine kinase-MB peak values were significantly increased in patients with major vessel disease and reduced left ventricular function (92 +/- 53 U/l versus 67 +/- 25 U/l). Both CK and CK-MB values were significantly higher in patients with aortic cross-clamp times of more than 1 h than in patients with shorter clamping times (661 +/- 188 and 78 +/- 40 U/l versus 500 +/- 200 and 57 +/- 24 U/l). Patients with 22 +/- 3 degrees C myocardial temperature before terminal cardioplegia had significantly elevated CK as compared to patients with temperatures of 15 +/- 2 degrees C (665 +/- 185 U/l versus 510 +/- 211 U/l). However, enzyme peak values had only poor predictive power for postoperative ECG changes, suggesting that enzyme peaks were not necessarily a sign of perioperative ischemia. Patients with major vessel disease and reduced myocardial function, with aortic cross-clamp time of more than 1 h and/or inadequate intraoperative myocardial cooling may be highly susceptible to global ischemia and operative procedures, and therefore show elevated peak enzyme levels shortly after surgery. In contrast, elevated myoglobin peaks within 1 h after aortic declamping were significantly correlated to perioperative signs of transient ischemia (P < 0.02).
...
PMID:Perioperative myocardial injury with different modes of antegrade and retrograde cardioplegic delivery. 866 19

Ischemic preconditioning has not been assessed in an experimental model for myocardial preservation during heart transplantation. Using isolated working rat hearts, ischemic preconditioning was investigated as an adjunct to isolated hypothermic (group 1), crystalloid (group 2: University of Wisconsin solution; group 3: St. Thomas' Hospital cardioplegic solution II; group 4: Bretschneiders' cardioplegic solution), and noncrystalloid (group 5: cold blood cardioplegia) preservation during a 10-hr period of global ischemia at 4 degrees C. After acquisition of functional baseline data, ischemic preconditioning was induced with one cycle of 5 min of normothermic ischemia and 5 min of reperfusion before induction of global hypothermic ischemia (n= 10/group). Nonpreconditioned hearts (n= 10/group) were assessed for control. Ischemic preconditioning improved postischemic: functional recovery. Thus, aortic flow after 60 min of reperfusion recovered to 0%, 8%, 0%, 1% and 0% in control groups 1 to 5 without ischemic preconditioning and 21%, 25%, 10%, 8%, and 3% in groups 1 to 5 with ischemic preconditioning. The same pattern of recovery was observed in regard to postischemic maximum developed left ventricular pressure, which recovered to 21%, 56%, 30%, 36%, and 19% in groups 1 to 5 without preconditioning and 46%, 75%, 49%, 40%, and 47% in the corresponding groups with ischemic preconditioning. High-energy phosphate contents were not significantly different between preconditioned hearts and corresponding nonpreconditioned control hearts. Creatine kinase leakage during early reperfusion was found to be reduced with ischemic preconditioning. Thus, we have demonstrated that ischemic preconditioning can improve contractile function after global hypothermic ischemia in the isolated rat heart and we have shown that this protection is additive to that of hypothermia-induced protection during global ischemia at 4 degrees C. This endogenous mechanism of cardioprotection was effective regardless of whether preservation was accomplished using cardioplegic solution or topical hypothermia alone. This may have clinical implications in myocardial preservation for heart transplantation.
...
PMID:Ischemic preconditioning enhances donor heart preservation. 869 37

The aim of the present study was to evaluate the effects of a single dose of nifedipine on myocardial stunning in isolated rabbit hearts. Hearts from rabbits pretreated with a single dose of 20 mg of nifedipine (NIF group) 1-4 h before isolation were compared to control hearts in their response to 15 min of global ischemia (37 degrees C) followed by 30 min of reperfusion. Both experimental groups showed similar baseline cardiac contractility. At the end of the reperfusion period in the control group, isovolumic left ventricular developed pressure (LVDP) and +dP/dtmax had stabilized at 45 +/- 2 and 48 +/- 2% of preischemic values respectively and in the NIF group LVDP stabilized at 63 +/- 6 and +dP/dtmax at 66 +/- 6% (P < 0.05 with respect to the control group). Left ventricular end diastolic pressure (LVEDP) values were significantly lower at the end of reperfusion in the NIF group compared to the controls (36.8 +/- 5.5 mmHg vs 53.4 +/- 3.9 mmHg, P < 0.05). The early impairment of the time constant of relaxation (tau) observed in control hearts was attenuated by pretreatment with nifedipine (control delta tau = 55 +/- 10 ms; NIF group delta tau = 29 +/- 5 ms, P < 0.05). Tissue ATP and creatine phosphate (CP) levels in the control group at the end of reperfusion were 6.9 +/- 0.7 and 8.7 +/- 0.7 mumol/g dry tissue, respectively; in the NIF group ATP and CP levels were significantly higher, 9.2 +/- 0.7 and 11.5 +/- 0.9 mumol/g dry tissue respectively (P < 0.05). Creatine kinase (CK) and lactate dehydrogenase (LDH) leakage during reperfusion were significantly higher in the control group (CK = 120 +/- 15 mU/ml and LDH = 60 +/- 8 mU/ml) compared to the NIF group (CK = 82 +/- 5 mU/ml and LDH = 41 +/- 2 mU/ml, P < 0.05). Our results demonstrate that pretreatment with a single oral dose (20 mg) of nifedipine attenuates systolic and diastolic functional alterations as well as the metabolic impairment associated with stunning in the isolated rabbit heart.
...
PMID:Protective effect of nifedipine on myocardial stunning in isolated rabbit hearts: role of high energy phosphates stores. 879 16

We examined whether or not alpha 1-adrenergic stimulation increases the tolerance of the heart to ischemia using a hypoxia-reoxygenation model of cardiac myocytes. After exposure to norepinephrine (NE; 0.2 microM) for 24 h, the manganese superoxide dismutase (Mn-SOD) content and activity in the cells were increased from 0.61 +/- 0.03 to 0.87 +/- 0.04 microgram/dish and 22 +/- 1 to 55 +/- 4 U/dish, respectively. The specific activity of Mn-SOD was also increased from 36 to 63 U/microgram Mn-SOD protein after the stimulation with NE. Prazosin (2 microM) abolished the increase in Mn-SOD activity (U/mg total protein). Creatine kinase (CK) release after hypoxia (PO2 7 mmHg; 3 h)-reoxygenation (1 h) from cells pretreated with NE in the presence of propranolol and yohimbine for 24 h was attenuated by 48% compared with that from cells without NE stimulation. When antisense oligodeoxyribonucleotides to Mn-SOD were added to myocyte cultures, the increase in Mn-SOD activity (U/mg total protein) and the attenuation of CK release after the addition of NE in the presence of propranolol and yohimbine were not observed. These results suggest that alpha 1-adrenergic stimulation increases the tolerance of myocytes to hypoxia through induction and activation of Mn-SOD.
...
PMID:Alpha 1-adrenergic stimulation induces cardiac tolerance to hypoxia via induction and activation of Mn-SOD. 889 28


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---