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)

Thirty-three canine hearts were isolated after initial cardioplegia and preserved for 6 hours in 4 degrees C saline solution with intermittent infusion of cardioprotective solution every hour. Reperfusion was observed for 2 hours under normothermic cross-circulation. Hearts were divided into five groups depending on the agent(s) added to the K(+)-Mg2+ cardioplegic solution (K(+)-Mg(2+)-CP) infused. Control hearts (n = 6) received K(+)-Mg(2+)-CP solution alone; group I (n = 7) received lidocaine, 200 mg/L, added to the K(+)-Mg(2+)-CP solution; group II (n = 7) received betamethasone (250 mg/L) added to the formula for group I; group III (n = 6) received diltiazem (200 micrograms/L) added to the formula for group II; group IV (n = 7) received aprotinin (150 KIU/L) added to the formula of group III. Coronary sinus MB fraction of creatine kinase level was significantly decreased at 60 and 120 minutes of reperfusion in group II, as was mitochondrial aspartate aminotransferase level at 2 hours of reperfusion. Lysosomal enzyme release decreased in group IV. Myocardial adenosine triphosphate levels and total adenine nucleotides showed no significant difference among the groups at the end of reperfusion; however, myocardial adenosine diphosphate and adenosine monophosphate levels during reperfusion increased significantly in group I, and myocardial adenosine diphosphate and adenosine monophosphate levels at the end of reperfusion in groups I and IV were significantly higher than those of the control. Calcium overload, which was lowest in group II, was not completely prevented during reperfusion in any group. Left ventricular end-systolic pressure volume relationship in group II showed the "best" functional recovery. In addition, the ultrastructure of the left ventricular myocardium was well preserved in all groups. These results suggest that membrane stabilization with lidocaine and betamethasone affords beneficial effects on myocardial biochemical and functional viability. Diltiazem appears to be less effective in preventing calcium overload during ischemia-reperfusion, and protease inhibition with aprotinin (150 KIU/ml) seems to be highly effective in suppressing lysosomal enzyme activation-release and maintaining myocardial adenosine diphosphate and adenosine monophosphate levels.
 ...
PMID:Heart preservation: analysis of cardioprotective infusate characteristics. Membrane stabilization, calcium antagonism, and protease inhibition on myocardial viability: a biochemical, ultrastructural, functional study. 137 28

The ability of diltiazem and/or desferrioxamine to enhance the recovery of cardiac contractile function during reperfusion after prolonged hypothermic storage was assessed. Isolated rat hearts were arrested with St. Thomas' Hospital Cardioplegic Solution and stored for 10 h at 4 degrees C. Reperfusion in the Langendorff mode was initially carried out with crystalloid perfusate with or without added diltiazem (0.5 mumol/l) and/or desferrioxamine (15, 50, 100, 150 or 250 mumol/l). After 15 min the drugs were discontinued and the hearts were perfused for a further 45 min. Diltiazem reduced leakage of creatine (CK) kinase during the first 15 min of reperfusion from 102 +/- 8 IU/15 min/g dry wt to 67 +/- 9 IU/15 min/g dry wt (P less than 0.05). However, during the subsequent period of diltiazem-free perfusion, CK leakage was similar to control values (131 +/- 24 vs 142 +/- 34 IU/45 min/g dry wt, respectively). After 1 h of reperfusion there was no significant difference in total CK leakage between the diltiazem and the control groups (198 +/- 32 vs 244 +/- 39 IU/60 min/g dry wt, respectively). Desferrioxamine had no effect on CK leakage at any of the doses studied. Diltiazem significantly reduced leakage of enzyme during the initial reperfusion phase when combined with desferrioxamine; however, as with diltiazem alone, this protection was lost after the drug was withdrawn. Post-ischemic contents of adenosine triphosphate and creatine phosphate were similar in all groups as was the final recovery of function, as assessed by left ventricular developed pressure at an end-diastolic pressure of 5 mmHg. In conclusion, neither diltiazem nor desferrioxamine nor both together could be shown to confer benefit during reperfusion after long-term storage.
 ...
PMID:Diltiazem and/or desferrioxamine administered at the time of reperfusion fail to improve post-ischemic recovery in the isolated rat heart after long-term hypothermic storage. 228 82

Oxygen-derived free radicals and intracellular calcium overload have been implicated as mediators of myocardial ischemia/reperfusion injury. We hypothesized that free radical scavengers or calcium channel blockers could enhance the protection afforded the isolated, working rat heart by crystalloid cardioplegia against this type of injury at 37 degrees C. Hearts from 42 male rats in seven groups (n = 6) were studied in an isolated, working heart preparation measuring aortic flow (ml/min/gm dry wt), peak systolic pressure (mm Hg), coronary artery flow (ml/min/gm dry wt), and calculated coronary vascular resistance (dyne.sec.cm-5/gm dry wt). Creatine kinase and lactate dehydrogenase release were measured before ischemia and at various times during the postischemic reperfusion period. Time-matched control hearts (group 1) were perfused for 2 hours. After finding that 30 minutes of ischemia and 10 minutes of reperfusion (group 2) produced significant (p less than 0.01) functional impairment that was completely protected (group 3) by a preischemic bolus of St. Thomas' Hospital cardioplegic solution, we again found significant (p less than 0.01) functional impairment after 40 minutes of ischemia and 10 minutes (group 4) or 20 minutes (group 5) of reperfusion despite a preischemic bolus of St. Thomas' Hospital cardioplegic solution. Diltiazem (10 mg/L) plus St. Thomas' Hospital cardioplegic solution (group 6) did not significantly (p less than 0.01) enhance functional recovery. Addition of superoxide dismutase plus catalase (200 microns/ml) (group 7) produced marked improvement in functional recovery that did not differ significantly (p less than 0.01) from control results (group 1). The creatine kinase and lactate dehydrogenase data strongly supported the preceding functional data. Coronary flow and vascular resistance were not significantly (p less than 0.01) changed from control values in any group. We conclude that the addition of superoxide dismutase and catalase but not diltiazem to St. Thomas' Hospital cardioplegic solution can significantly enhance myocardial protection against normothermic ischemia/reperfusion injury. This implicates oxygen-derived free radicals as mediators of this type of injury.
 ...
PMID:Enhancement of crystalloid cardioplegic protection against global normothermic ischemia by superoxide dismutase plus catalase but not diltiazem in the isolated, working rat heart. 336 28

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control (10 min), normoxic cardioplegia (10 min), intermittent global ischemic arrest (two 15-min periods separated by 2 min infusion of the normoxic cardioplegic perfusate), and normoxic postischemic control reperfusion (60 min). Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl2, and 20 mM MgCl2 with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of 31P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P less than 0.01) that persisted throughout the first 50 min of postischemic reperfusion. Diltiazem in combination with magnesium cardioplegia was detrimental to postischemic functional recovery, despite a rapid restoration of high-energy phosphate stores. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically. The mechanistic basis and drug specificity of this response require further clarification. The present findings appear to exclude ATP and PCr production, and structural causes as the basis for the observed aberrant functional recovery from global ischemia of magnesium plus diltiazem-arrested hearts.
 ...
PMID:Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia. 371 20

The effect of diltiazem on post-ischemic metabolic and functional recovery was investigated in regionally ischemic dog hearts. The duration of ischemia was 60 min, followed by 60 min of reperfusion. Diltiazem (bolus injection of 0.1 mg X kg-1 body weight prior to ischemia, followed by a continuous infusion of 0.1 mg X kg-1 X h-1) had no effect on residual coronary flow in the centre of the ischemic area, but blunted the reactive hyperemia response after restoration of flow. The drug partially prevented the depletion of ATP and glycogen in the severely underperfused subendocardial layers, i.e. when residual flow was below 0.1 ml X min-1 X g-1. Reduction of the content of these substances in the subepicardial layers was moderate and not influenced by diltiazem. Segment shortening in the subepicardial layers disappeared whereas segment lengthening was observed in the subendocardial layers during the ischemic period. Diltiazem did not prevent the loss of contractile function. Despite an initial restoration of contractile function within 10 min after reperfusion, no significant beneficial effect of diltiazem treatment on mechanical function of the reperfused area was present thereafter.
 ...
PMID:The effect of diltiazem on myocardial recovery after regional ischemia in dogs. 373 98

To evaluate the effects of pharmacologic vasodilatation on glycerol-induced acute renal failure, we studied untreated animals and those given Captopril and Diltiazem at periods ranging from 30 minutes to four weeks after the onset of acute renal failure. At each time frame, comparative coded assessments of renal function, histology, and microangiography were performed. Diltiazem, a calcium channel blocker, significantly reduced the severity of the renal failure, decreased the extent of tubular cell necrosis, and was associated with a more rapid histologic and functional recovery. Captopril, an angiotensin converting enzyme inhibitor, did not influence renal function or pathology throughout the four-week observation period. Microangiography revealed marked differences among the experimental groups. Most notably, there was better visualization of the microvasculature in Diltiazem-treated kidneys at one and two weeks. However, at four weeks, all groups showed similar, severe microangiographic abnormalities. Diltiazem offers significant protection against glycerol-induced acute renal failure in rats. Its mechanism of action in this context remains unknown. Renal function and pathology do not correlate well with microangiographic perfusion patterns in this model of acute renal failure.
 ...
PMID:The effects of diltiazem and captopril on glycerol-induced acute renal failure in the rat. Functional, pathologic, and microangiographic studies. 390 88

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood-potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing diltiazem, 400 micrograms per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 micrograms/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 micrograms/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used. Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak - dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p less than 0.025) and compliance decreased (p less than 0.02). In both groups, coronary vascular resistance declined (p less than 0.001) and recovery of adenosine triphosphate (p less than 0.001), adenosine diphosphate (p less than 0.025), and the adenosine pool (p less than 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2. Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.
 ...
PMID:Cold blood-diltiazem cardioplegia. 706 65