Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the nature of ischemia- and reperfusion-induced lipid changes and their consequences for myocardial function and integrity, Krebs-Henseleit perfused, isolated, working rat hearts were treated with nicotinic acid or mepacrine, putative inhibitors of triacylglycerol and phospholipid hydrolysis, respectively. In non-treated hearts 60 min ischemia resulted in a marked rise in myocardial fatty acid (FA) content. The FA content sharply increased further during 30 min reperfusion. Seven out of 16 (44%) hearts fibrillated continuously during reperfusion. Post-ischemic recovery of cardiac output (CO) of the non-fibrillating hearts amounted to 68 +/- 15% of the preischemic value. Nicotinic acid (10 microM) significantly reduced FA accumulation during ischemia (P less than 0.05), but not during reperfusion (0.05 less than P less than 0.10). Post-ischemic recovery of CO was improved (87 +/- 12%). This was neither associated with preservation of myocardial adenine nucleotide content, nor significant reduction of enzyme release. Mepacrine (1 microM) completely abolished reperfusion arrhythmias and improved recovery of CO (88 +/- 7% of pre-ischemic value). The reduction of FA content in ischemic and reperfused hearts did not reach the level of significance. Enzyme release was not attenuated. At 10 microM, mepacrine completely prevented accumulation of FAs during ischemia and reperfusion, abolished reperfusion-arrhythmias, and reduced enzyme release. No concomitant preservation of adenine nucleotides was observed. In conclusion, nicotinic acid and mepacrine are able to reduce ischemia- and reperfusion-induced changes in myocardial lipid metabolism. In addition, both drugs improve post-ischemic functional recovery. It remains to be established whether these effects are causally related.
 ...
PMID:Effects of nicotinic acid and mepacrine on fatty acid accumulation and myocardial damage during ischemia and reperfusion. 232 35

Halothane has been shown to be a powerful myocardial protectant during normothermic cardioplegic arrest and subsequent reperfusion. In view of its multiple effects on cellular Ca2+ movements and the role of this ion in ischemia-reperfusion injury, the questions of whether halothane is capable of maximally protecting the heart or whether combination therapy of halothane with other Ca2+ blocking agents may be more effective arose. Therefore, the effects of combination therapy with halothane and a calcium antagonist (nifedipine), or a Na+/H+ inhibitor (HOE 694), or a Na+/Ca2+ inhibitor (quinacrine) on postcardioplegic functional recovery were evaluated. The isolated perfused rat heart subjected to 45 minutes normothermic cardiac arrest was used as an experimental model. Dose-response curves were performed for each drug. Using the optimal dosage for each drug, the following results were obtained: (1) Nifedipine (10(-7) M; administered retrogradely 10 minutes before and after cardioplegia) and halothane (1.5% administered during cardioplegia), when administered separately, improved functional recovery. Combination therapy did not further improve protection. (2) HOE 694 (10(-7) M) or quinacrine (10(-9) M) improved post-cardioplegic functional recovery when added for 2 minutes at the onset of reperfusion. Simultaneous administration of HOE 694 and 1.5% halothane was the only combination that yielded additive protection. (3) Quinacrine, a phospholipase and Na+/Ca2+ exchanger inhibitor, appeared to be the most powerful drug used. In summary, the results obtained indicate that interventions aimed at preventing intracellular Ca2+ overload improve recovery after cardioplegic arrest. The beneficial effects of halothane could be further improved by HOE 694.
 ...
PMID:Postcardioplegic myocardial recovery: effects of halothane, nifedipine, HOE 694, and quinacrine. 978 6