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)

We have compared the protective properties of three cardioplegic solutions (St. Thomas' Hospital, University of Wisconsin, and Bretschneider) for the long-term hypothermic preservation of the rat heart. Hearts (n = 8 per group) were excised and arrested by an infusion (10 ml at 4 degrees C) of cardioplegic solution. After 4, 6, or 8 hours of storage at 4 degrees C, they were reperfused in the Langendorff mode for 15 minutes and then in the working mode for 20 minutes. After 4 hours of storage, postischemic cardiac output in the St. Thomas' and Wisconsin groups was 68.8 +/- 4.6 and 63.7 +/- 3.0 ml/min, respectively (NS); nonischemic aerobic control cardiac output was 83.2 +/- 2.6 ml/min. In the Bretschneider group, cardiac output was only 43.4 +/- 3.6 ml/min (p less than 0.05 compared to the other groups). Extending storage to 6 or 8 hours led to further decreases in recovery of function in all groups (cardiac output in the St. Thomas' and Wisconsin groups was 53.7 +/- 3.2 and 52.2 +/- 5.1 ml/min after 6 hours and 39.9 +/- 2.2 and 45.8 +/- 2.5 ml/min after 8 hours, respectively; NS). With the Bretschneider solution the cardiac output was again lower (37.6 +/- 3.0 and 22.3 +/- 4.1 ml/min, respectively). Creatine kinase leakage tended to be greater in the Bretschneider group, but adenosine triphosphate and creatine phosphate contents were well preserved in all groups. In further studies, hearts (n = 8 per group) were infused with the three solutions and stored at 4 degrees C for 8 or 10 hours; they were then heterotopically transplanted into the abdomens of homozygous recipients. After 24 hours of reperfusion, the hearts were excised and taken for ex vivo functional and metabolic studies. Recovery of contractile function was similar in all groups, but the tissue content of adenosine triphosphate tended to be greater in the St. Thomas' and Wisconsin groups (15.0 +/- 1.5 and 14.7 +/- 1.0 mumol/gm dry weight in the 8-hour storage groups and 12.1 +/- 1.2 and 11.7 +/- 0.8 mumol/gm dry weight in the 10-hour storage groups, respectively) than in the Bretschneider groups (12.3 +/- 0.9 and 9.1 +/- 1.6 mumol/gm dry weight, respectively). Creatine phosphate content recovered completely in all groups. We conclude that all three solutions afford similar protection to the hypothermically stored rat heart, but that the St. Thomas' Hospital and University of Wisconsin solutions are marginally superior to the Bretschneider solution.
 ...
PMID:Long-term hypothermic storage of the mammalian heart for transplantation: a comparison of three cardioplegic solutions. 149 25

The concentration of calcium (1.2 mmol/L) in clinical St. Thomas' Hospital cardioplegic solution was chosen several years ago after dose-response studies in the normothermic isolated heart. However, recent studies with creatine phosphate in St. Thomas' Hospital solution demonstrated that additional myocardial protection during hypothermia resulted principally from its calcium-lowering effect in the solution. The isolated working rat heart model was therefore used to establish the optimal calcium concentration in St. Thomas' Hospital solution during lengthy hypothermic ischemia (20 degrees C, 300 minutes). The calcium content of standard St. Thomas' Hospital solution was varied from 0.0 to 1.5 mmol/L in eight treatment groups (n = 6 for each group). During ischemia, hearts were exposed to multidose cardioplegia (3 minutes every 30 minutes). Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase and the time to return of sinus rhythm during the reperfusion period were also measured. These dose-response studies during hypothermic ischemia revealed a broad range of acceptable calcium concentrations (0.3 to 0.9 mmol/L), which appear optimal in St. Thomas' Hospital solution at 0.6 mmol/L. This concentration improved the postischemic recovery of aortic flow from 22.0% +/- 5.9% with control St. Thomas' Hospital solution (calcium concentration 1.2 mmol/L) to 86.0% +/- 4.0% (p less than 0.001). Other indices of functional recovery showed similar dramatic results. Creatine kinase release was reduced 84% (p less than 0.01) in the optimal calcium group. Postischemic reperfusion arrhythmias were diminished with the loser calcium concentration, with a significant decrease in the time between initial reperfusion until the return of sinus rhythm. In contrast, acalcemic St. Thomas' Hospital solution precipitated the calcium paradox with massive enzyme release and no functional recovery. Unlike prior published calcium dose-response studies at normothermia, these results demonstrate that the optimal calcium concentration during clinically relevant hypothermic ischemia is considerably lower than that of normal serum ionized calcium (1.2 mmol/L) and appears ideal at 0.6 mmol/L to realize even greater cardioprotective and antiarrhythmic effects with St. Thomas' Hospital solution.
 ...
PMID:Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution improves protection during hypothermic ischemia. 199 42

Isolated hearts from rabbits, hamsters, ferrets, gerbils, rats, mice and guinea pigs were used to investigate species differences in (i) stability during aerobic perfusion, (ii) susceptibility to ischemic injury and (iii) responsiveness to cardioplegic protection. During 120 minutes of continuous aerobic perfusion, the rate of functional deterioration differed between species. The rabbit was the most stable and the guinea pig the least: the mean +/- SEM of the left ventricular developed pressure falling, after 120 minutes of perfusion, to 82 +/- 4% and 60 +/- 6%, respectively. In studies with 30 minutes of ischemia and 60 minutes of reperfusion, the developed pressure recovered to 72 +/- 2, 71 +/- 2, 65 +/- 3, 64 +/- 2, 58 +/- 3, 50 +/- 8 and 50 +/- 2% of its pre-ischemic value in the rabbit, hamster, ferret, gerbil, rat, mouse and guinea pig, respectively. With 60 minutes of ischemia, the recovery of developed pressure in the guinea pig, rabbit, rat, mouse, hamster, ferret and gerbil was 5 +/- 1, 19 +/- 2, 22 +/- 3, 30 +/- 5, 55 +/- 4, 60 +/- 2 and 45 +/- 5%, respectively. Creatine kinase leakage and changes in tissue metabolite content generally reflected the degree of functional injury. In further studies, groups of 6 hearts were infused for 2 minutes with St. Thomas' Hospital Cardioplegic Solution, then subjected to 30 minutes of ischemia. Cardioplegia improved the recovery of developed pressure in the rabbit, hamster, gerbil, rat and mouse (from 72 +/- 2, 71 +/- 2, 64 +/- 2, 58 +/- 3 and 50 +/- 8% to 82 +/- 3, 103 +/- 3, 84 +/- 4, 77 +/- 2 and 78 +/- 5%, respectively; p less than 0.05 for each species). However, no protection was observed in the ferret and guinea pig (65 +/- 3 and 50 +/- 2% versus 66 +/- 3 and 47 +/- 6%, respectively; p = NS). With cardioplegia, tissue high-energy phosphates increased significantly in all species except the gerbil. Rat and guinea pig hearts were taken for time-response studies (ischemia for 15, 20, 30, 45, 50 and 60 minutes in the rat and 15, 30, 45 and 60 minutes in the guinea pig) with or without cardioplegia. In the rat, cardioplegia improved recovery over an ischemic time-window of 20-45 minutes, but in the guinea pig no improvement was detected. Creatine kinase leakage reflected the patterns of functional recovery. In contrast, high-energy phosphates were preserved better in both species after 30 minutes of ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Species differences in susceptibility to ischemic injury and responsiveness to myocardial protection. 210 1

The effect of oxygenation (100% oxygen) of the St. Thomas' Hospital cardioplegic solutions No. 1 (MacCarthy) and No.2 (Plegisol, Abbott Laboratories, North Chicago, Ill.) was examined in the isolated working rat heart subjected to long periods (3 hours for studies with solution No. 1 and 4 hours for studies with solution No. 2) of hypothermic (20 degrees C) ischemic arrest with multidose (every 30 minutes) cardioplegic infusion. At the aortic infusion point the oxygen tension of the oxygenated solutions (measured at 20 degrees C) was in the range of 320 to 560 mm Hg whereas that of the nonoxygenated solutions was less than 150 mm Hg. Twenty hearts (10 oxygenated and 10 nonoxygenated) were studied for each solution. The studies with solution No. 1 demonstrated that oxygenation led to a significant (p less than 0.05) reduction in the incidence of persistent ventricular fibrillation during postischemic reperfusion. Oxygenation of the cardioplegic solution also improved postischemic functional recovery so that the recovery of aortic flow was improved from 18.7% +/- 8.9% (of its preischemic control level) in the nonoxygenated group to 54.6% +/- 6.6% in the oxygenated group (p less than 0.025). Creatine kinase leakage was also significantly reduced from 27.5 +/- 4.8 to 9.9 +/- 0.6 IU/15 min/gm dry weight (p less than 0.005). Studies with solution No. 2 indicated that protection was better than with solution No. 1, even in the absence of oxygenation. A better degree of functional recovery was obtained after 4 hours of arrest with solution No. 2 than that obtained after only 3 hours of arrest with solution No. 1, and persistent ventricular ventricular fibrillation was never observed with solution No. 2. However, despite the superior performance with solution No. 2, further improvements could be obtained by oxygenation, with that time from the onset of reperfusion to the return of regular sinus rhythm being reduced from 55 +/- 8 to 35 +/- 2 seconds (p less than 0.01), postischemic recovery of aortic flow increasing from 59.8% +/- 7.4% to 85.7% +/- 2.5% (p less than 0.005), and creatine kinase leakage being reduced from 38.1 +/- 7.3 to 16.2 +/- 1.5 IU/15 min/gm dry weight (p less than 0.005). It is concluded that oxygenation of the St. Thomas' Hospital cardioplegic solutions improves their ability to protect the heart against long periods of ischemia and that this is manifested by improved postischemic electrical stability, functional recovery, and reduced creatine kinase leakage.
 ...
PMID:Improved myocardial protection by oxygenation of St. Thomas' Hospital cardioplegic solutions. Studies in the rat. 333 23

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

One or more brief periods of ischemia, termed preconditioning, dramatically limits infarct size and reduces intracellular acidosis during subsequent ischemia, potentially via enhanced sarcolemmal proton efflux mechanisms. To test the hypothesis that preconditioning increases the functional activity of sodium-dependent proton efflux pathways, isolated rat hearts were subjected to 30 min of global ischemia with or without preconditioning. Intracellular sodium (Nai) was assessed using 23Na magnetic resonance spectroscopy, and the activity of the Na-H exchanger and Na-K-2Cl cotransporter was measured by transiently exposing the hearts to an acid load (NH4Cl washout). Creatine kinase release was reduced by greater than 60% in the preconditioned hearts (P < 0.05) and was associated with improved functional recovery on reperfusion. Preconditioning increased Nai by 6.24 +/- 2.04 U, resulting in a significantly higher level of Nai before ischemia than in the control hearts. Nai increased significantly at the onset of ischemia (8.48 +/- 1.21 vs. 2.57 +/- 0.81 U, preconditioned vs. control hearts; P < 0.01). Preconditioning did not reduce Nai accumulation during ischemia, but the decline in Nai during the first 5 min of reperfusion was significantly greater in the preconditioned than in the control hearts (13.48 +/- 1.73 vs. 2.54 +/- 0.41 U; P < 0.001). Exposure of preconditioned hearts to ethylisopropylamiloride or bumetanide in the last reperfusion period limited in the increase in Nai during ischemia and reduced the beneficial effects of preconditioning. After the NH4Cl prepulse, preconditioned hearts acidified significantly more than control hearts and had significantly more rapid recovery of pH (preconditioned, delta pH = 0.35 +/- 0.04 U over 5 min; control, delta pH = 0.15 +/- 0.02 U over 5 min). This rapid pH recovery was not affected by inhibition of the Na-K-2Cl cotransporter but was abolished by inhibition of the Na-H exchanger. These results demonstrate that preconditioning alters the kinetics of Nai accumulation during global ischemia as well as proton transport after NH4Cl washout. These observations are consistent with stimulation of the Na-K-2Cl cotransporter and Na-H exchanger by preconditioning.
 ...
PMID:Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts. 765 18

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

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

Preconditioning is commonly induced by a brief ischemic insult; myocardial stretch can trigger this protection by an unknown mechanism. Myocardial stretch preconditions the in vivo canine heart; however, the existence of a stretch-induced protection in the rat heart remains unknown. The purpose of this study was to test this myocardial protection induced, in isolated working rat heart, by global ischemia and stretch initiated by a transient increase in the left ventricle (LV). Isolated rat hearts underwent 30 min of global ischemia followed by 30 min of reperfusion. Before this, hearts received a 15-min period of either no intervention (control; C), 5 min of global ischemia + 10 min of reperfusion (preconditioning; PC) or 5 min of stretch + 10 min with no intervention (stretch; S). Stretch was induced by a transient increase in LV preload from 5 to 20 cm H2O. LV work started under a afterload of 80 cm H2O. Control, PC, and S hearts received either no drug (untreated) or staurosporine (50 nM), a protein kinase C inhibitor, before the "preconditioning" period. Creatine kinase (CK) release, ventricular fibrillation during reperfusion, and postischemic recovery of contractile function (aortic flow) were the end points of the study. In the S group, the abrupt increase in preload resulted in a significant increase of aortic flow (42 +/- 2 to 47 +/- 2 ml/min; p < 0.05). During the 30-min reperfusion period, control hearts displayed a poor recovery of contractile functions (8 +/- 3 ml/min, 30 min after reflow, versus 40 +/- 2 ml/min at baseline; p < 0.05). Both untreated PC and S groups exhibited a significant reduction in CK release, incidence of ventricular fibrillation (55% of control hearts developed persistent VF vs. 6% in both the PC and S groups), and postischemic dysfunction during reperfusion (p < 0.05 vs. control). Staurosporine prevented these beneficial effects in PC and S groups. Our study suggests that myocardial protection can be induced by stretch in the isolated working rat heart, likely through activation of protein kinase C. In conclusion, our results show that ischemic preconditioning and stretch had comparable favorable effect on functional recovery after a sustained ischemic insult in the isolated rat heart.
 ...
PMID:Beneficial actions of preconditioning and stretch on postischemic contractile function of isolated working rat heart: effects of staurosporine. 926 46

Preservation of the right-ventricular (RV) myocardium is a clinical challenge especially in patients with occluded right coronary artery, in whom antegrade cardioplegia cannot reach areas distal to the stenosis. Retrograde administration of cardioplegia has been thought to overcome the problem, but it has been blamed for inadequate distribution to the RV and possibly poorer functional recovery of this ventricle. Adapting the hypothesis that warm blood cardioplegia may offer better distribution and a more effective supply of oxygen to the arrested heart, we compared RV function in a randomised trial in patients with significant right and left coronary artery disease, after either warm continuous (warm group, n = 15) or intermittent cold (cold group, n = 14) retrograde blood cardioplegia. Right-ventricular function was assessed by determining the ejection fraction (fast-response thermodilution) and preload-related RV stroke work in repeated measurements. The RV ejection fraction remained steady in the warm group during the postoperative course, while it declined significantly in the cold group after operation and differed from that in the warm group until the second postoperative day (p < 0.05-0.001). The ratio of RV stroke work to right atrial pressure was greater postoperatively in the warm than in the cold group until 6 hours after cardiopulmonary bypass (p < 0.05-0.01). Creatine kinase cardiac isoenzyme release was greater in the cold group (p < 0.01). The relationship between left-ventricular stroke work and corresponding preload did not differ between the groups. It can be concluded that recovery of RV function after coronary surgery was better in terms of ejection fraction and preload-related stroke work with warm continuous cardioplegia than with intermittent cold cardioplegia, this along with lower cardiac enzyme release suggesting better RV protection.
 ...
PMID:Right ventricle is protected better by warm continuous than by cold intermittent retrograde blood cardioplegia in patients with obstructed right coronary artery. 932 20


1 2 Next >>