Recovery Of Developed Force Research Articles

Possible role of mitochondrial K-ATP channel and nitric oxide in protection of the neonatal rat heart

Cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by mitochondrial-K-ATP channels and nitric oxide (NO). During early developmental period, rat hearts exhibit higher resistance to ischemia–reperfusion (I/R) injury and their resistance cannot be further increased by IPC or IPoC. Therefore, we have speculated, whether mechanisms responsible for high resistance of neonatal heart may be similar to those of IPC and IPoC. To test this hypothesis, rat hearts isolated on days 1, 4, 7, and 10 of postnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured. Hearts were exposed to 40 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC was induced by 5 cycles of 10-s ischemia. Mito-K-ATP blocker (5-HD) was administered 5 min before ischemia and during first 20 min of reperfusion. Another group of hearts was isolated for biochemical analysis of 3-nitrotyrosine, and serum samples were taken to measure nitrate levels. Tolerance to ischemia did not change from day 1 to day 4 but decreased on days 7 and 10. 5-HD had no effect either on neonatal resistance to I/R injury or on cardioprotective effect of IPoC on day 10. Significant difference was found in serum nitrate levels between days 1 and 10 but not in tissue 3-nitrotyrosine content. It can be concluded that while there appears to be significant difference of NO production, mito-K-ATP and ROS probably do not play role in the high neonatal resistance to I/R injury.

Selenium protects the immature rat heart against ischemia/reperfusion injury

The aim of the study was to find out whether administration of selenium (Se) will protect the immature heart against ischemia/reperfusion.The control pregnant rats were fed laboratory diet (0.237 mg Se/kg diet); experimental rats received 2 ppm Na(2)SeO(3) in the drinking water from the first day of pregnancy until day 10 post partum. The concentration of Se in the serum and heart tissue was determined by activation analysis, the serum concentration of NO by chemiluminescence, cardiac concentration of lipofuscin-like pigment by fluorescence analysis. The 10 day-old hearts were perfused (Langendorff); recovery of developed force (DF) was measured after 40 min of global ischemia. In acute experiments, 10 day-old hearts were perfused with selenium (75 nmol/l) before or after global ischemia. Sensitivity to isoproterenol (ISO, pD(50)) was assessed as a response of DF to increasing cumulative dose.Se supplementation elevated serum concentration of Se by 16%. Se increased ischemic tolerance (recovery of DF, 32.28 +/- 2.37 vs. 41.82 +/- 2.91%, P < 0.05). Similar results were obtained after acute administration of Se during post-ischemic reperfusion (32.28 +/- 2.37 vs. 49.73 +/- 4.40%, P < 0.01). The pre-ischemic treatment, however, attenuated the recovery (23.08 +/- 3.04 vs. 32.28 +/- 2.37%, P < 0.05). Moreover, Se supplementation increased the sensitivity to the inotropic effect of ISO, decreased cardiac concentration of lipofuscin-like pigment and serum concentration of NO. Our results suggest that Se protects the immature heart against ischemia/reperfusion injury. It seems therefore, that ROS may affect the function of the neonatal heart, similarly as in adults.

Low-dose postoperative aprotinin reduces blood transfusion requirements in primary CABG patients on aspirin

treatment group and 1.29kO.18 in the placebo group p=O.OOl). No significant differences were seen in cardiac (p=O.17). Troponin I levels at 4 hours postoperatively index, or LVSWI between treatment groups. were 60.7k22.3 in the treatment group and 100.0&4.1 in Conclusions: CoQlo serum levels can be raised the placebo group (p=O.42). No differences were seen in significantly with 1 week of oral dosing. No effect of recovery of peak developed force after ischaemic stress CoQlO is seen on early postoperative recovery in this in muscle strips from treated and untreated patients in initial cohort of patients. lschaemia did not sufficiently this initial cohort of patients. Hypoxia resulted in a depress recovery of muscle strips to detect any treatment significant decrease in recovery of peak developed force differences. Hypoxia with pacing has been successful in in untreated muscle strips compared with the untreated reducing recovery of developed force and will be used in ischaemic muscle strips (47.8%*10.8% vs 85.6%&4.5%, the second cohort of patients.

Oral sulfonylurea hypoglycemic agents prevent ischemic preconditioning in human myocardium. Two paradoxes revisited.

Patients receiving oral hypoglycemic agents for diabetes mellitus are at increased risk of cardiovascular mortality. Oral hypoglycemic agents are inhibitors of the ATP-sensitive potassium (KATP) channel. Ischemic preconditioning is mediated by KATP channel activation. We therefore hypothesized that myocardium from patients taking long-term oral hypoglycemic agents would be resistant to the protection by ischemic preconditioning. Isolated human right atrial trabeculae were suspended in an organ bath at 37 degrees C, with field stimulation at 1 Hz. Control trabeculae were then subjected to 45 minutes of simulated ischemia (hypoxic, glucose-free buffer with pacing at 3 Hz) and 120 minutes of reperfusion. Ischemic preconditioned (IPC) trabeculae from patients without oral hypoglycemic therapy and from patients taking insulin (Ins+IPC) were given 5 minutes of simulated ischemia before this injury. Trabeculae (Oral Hypo+IPC) were obtained from patients taking long-term oral hypoglycemic agents and were also exposed to 5 minutes of simulated ischemia before this injury. Developed force (DF) was recorded. Recovery of DF relative to preischemic values was 28 +/- 4% in control trabeculae, whereas IPC trabeculae showed 52 +/- 5% recovery (P < .05 versus control). In patients receiving long-term oral hypoglycemic agents (Oral Hypo+IPC), recovery of DF was 27 +/- 3%, but in trabeculae from insulin-treated patients (Ins+IPC), it was 45 +/- 6%. Human myocardium from patients without long-term exposure to oral hypoglycemic agents is functionally protected by preconditioning. Long-term oral hypoglycemic intake blocks the protection by preconditioning. These data suggest that ischemic preconditioning in human myocardium relies on KATP channels, and long-term inhibition of KATP channels with oral hypoglycemic agents may explain the excess cardiovascular mortality in these patients.

The obligate role of protein kinase C in mediating clinically accessible cardiac preconditioning

Cardiac preconditioning is an adaptation of cardiomyocytes that promotes tolerance to a subsequent ischemic insult. Adenosine receptor signaling is proposed as a mediator of preconditioning, but its mechanism of protection remains unknown. We hypothesized that protection against hypoxia-reoxygenation (H/R) injury could be conferred in a rat ventricle by adenosine-mediated protein kinase C (PKC) activation and that adenosine-mediated cardioprotection could be extended to human ventricular muscle. Isolated rat and human ventricular muscle (VM) strips were subjected to 30 minutes of hypoxia and 60 minutes of reoxygenation (H/R control). The VM was pretreated with 125 mumol/L adenosine, an adenosine antagonist ((p-Sulfophenyl) theophylline [SPT] 50 mumol/L) and adenosine (adenosine + SPT), or with a PKC inhibitor (chelerythrine, 10 mumol/L) and adenosine (adenosine + chelerythrine) before H/R Developed force (DF) and tissue creatine kinase (CK) activity were assessed at end reoxygenation. Human trabeculae were obtained from diseased explanted hearts at cardiac transplantation and were also subjected to H/R injury. Human VM was pretreated with adenosine (125 mumol/L) before H/R injury. Results are expressed as mean +/- standard error of mean. In the rat, adenosine pretreatment conferred protection of DF against H/R injury (adenosine, 62% +/- 6%; H/R control, 27% +/- 2%, p < 0.05). Adenosine + SPT or adenosine + chelerythrine eliminated the functional recovery conferred by adenosine. This recovery of contractile function was associated with greater tissue CK activity (adenosine, 415 +/- 40 units/gm; H/R control, 78 +/- 13 units/gm, p < 0.05). The protective effects of adenosine against H/R were present in the human ventricle and with recovery of DF in adenosine (66% +/- 5%) and H/R control (24% +/- 4%), p < 0.05. Adenosine, a clinically accessible agonist, induces protection against H/R injury through a PKC-mediated mechanism in the rat ventricle. Further, the protection conferred by adenosine against H/R extends to the human ventricle.