Creatine phosphate: An additive myocardial protective and antiarrhythmic agent in cardioplegia

Robinson, Lary A.; Braimbridge, M. V.; Hearse, David J.; Jones, Robert H.

doi:10.1016/s0022-5223(19)37413-6

Cited by 80 publications

(7 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other investigators have attempted to stimulate myocardial adenine nucleotide biosynthesis directly by using pentoses, pentitols, and 5-aminoimidazoie-4-carboxamide riboside (AICAR) with variable results [12, 131. Finally, direct exogenous administration of the two major intracellular high-energy phosphate compounds, ATP and creatine phosphate, has been utilized in an attempt to benefit postischemic functional recovery in the myocardium [14,151. However,their utilization is hindered by the inability of these compounds, which are both very large and highly charged, to cross the cell membrane [ 161.…”

Section: Discussionmentioning

confidence: 99%

Effect of ATP synthesis promoters on postischemic myocardial recovery

Bolling

Bies

Bove

1990

Journal of Surgical Research

View full text Add to dashboard Cite

The use of cardioplegia during surgically induced ischemia greatly reduces myocardial metabolic requirements. However, adenosine triphosphate (ATP) depletion may occur, resulting in poor functional recovery after ischemia. This study investigated if augmentation of intracellular ATP could be achieved by delivering known ATP synthesis promoters (adenosine and/or phosphate) during cardioplegic arrest, and whether this could enhance myocardial functional and metabolic recovery following ischemia. Isolated, perfused rabbit hearts were subjected to 120 min of hypothermic (34 degrees C) cardioplegia-induced ischemia. Controls received St. Thomas cardioplegia (CTL); remaining hearts received cardioplegia containing 200 microM adenosine (ADO), or 25 microM phosphate (PO4), or both ADO and PO4. Following ischemia and reperfusion, recovery of developed pressure (%DP) and postischemic diastolic stiffness was significantly better in adenosine hearts when compared with control or PO4 hearts. To determine if ADO or PO4 minimized depletion of ATP during ischemia or accelerated synthesis of ATP in the postischemic period, nucleotide levels were obtained before, during, and after ischemia. During ischemia, ATP fell equally in all groups, indicating that ADO and PO4 did not alter ischemia-induced depletion of ATP. However, intracellular adenosine was augmented during ischemia in adenosine-treated hearts. Consequently, during reperfusion, ADO and ADO/PO4 hearts had significantly enhanced ATP levels, suggesting that augmenting myocardial adenosine accelerated synthesis of ATP postischemia. The addition of phosphate, a stimulus for ATP synthesis, did not augment postischemic ATP. In fact, the beneficial effect of adenosine may have been decreased when phosphate was added to adenosine. In conclusion, adenosine but not PO4 augments intracellular ATP by allowing better metabolic repletion following ischemia, thereby improving postischemic myocardial functional recovery.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of ATP synthesis promoters on postischemic myocardial recovery

Bolling

Bies

Bove

1990

Journal of Surgical Research

View full text Add to dashboard Cite

show abstract

“…During myocardial ischemia there is a rapid depletion of CP followed by a decrease of ATP (4). In addition, under hypothermic cardioplegic arrest and the following reperfusion, a degradation of these compounds has been reported (1) et al have shown that CP improves the myocardial protection in rat hearts ( 7). In a subsequent paper the same authors reported an additive effect of CP and ATP in Cardioplegic solution in a rat-heart model ( 8).…”

Section: Introductionmentioning

confidence: 99%

Biochemical and Functional Effects of Creatine Phosphate in Cardioplegic Solution during Aortic Valve Surgery - a Clinical Study

Thelin

Ronquist

et al. 1992

Thorac cardiovasc Surg

View full text Add to dashboard Cite

During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP.

show abstract

“…This co nd it ion may result in a p rocess di rected towards increased perm eabilit y to otherwi se impermeable so lutes (7 , 12 ), suc h as creat ine phosp hate. Th e explo itable effect o f crea t ine phosp hate ma y not necessa ri ly be exe rte d in th e cy to p las m. Instead , a meta boli c rol e o f thi s co m po u nd co uld be of importance in th e plasma m embran e itself (17) . T here a re severa l repo rts o n a n a n tia rr hy th mic e ffec t o f creat ine pho sphat e (6, 16,17).…”

Section: Discussionmentioning

confidence: 99%

“…Th e explo itable effect o f crea t ine phosp hate ma y not necessa ri ly be exe rte d in th e cy to p las m. Instead , a meta boli c rol e o f thi s co m po u nd co uld be of importance in th e plasma m embran e itself (17) . T here a re severa l repo rts o n a n a n tia rr hy th mic e ffec t o f creat ine pho sphat e (6, 16,17). In the pre sent study all hearts had to be defib ri llated a fter ische mi a becau se of ven t ricular fib rillation, but there wa s o nly one heart in th e co n tro l group th at did not ret u rn to sinus rh ythm.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that in the rat ATP both in a high and in a low dose enhances the myocardial protection by cardioplegia (10,20). Creatine phosphate has also been shown to improve the myocardial prot ection in rat hearts and the optim al dose in in vitro studies was 10 mmol/1 (10,17). In vivo studies on dog hearts showed protective effects of the agent (3).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Improved Myocardial Protection by Creatine Phosphate in Cardioplegic Solution. An In Vivo Study in the Pig During Normothermic Ischemia

Thelin¹,

Hultman²,

Ronquist³

et al. 1987

Thorac cardiovasc Surg

View full text Add to dashboard Cite

The effect of creatine phosphate in potassium cardioplegia was studied in a pig heart model in vivo. Fifteen pigs divided into two groups were placed on cardiopulmonary bypass and subjected to 1 hour of cardioplegic arrest at normothermia. In group I (control), in which a potassium cardioplegic solution was used, only two out of eight animals could successfully be weaned from bypass. In group II, on the other hand, in which creatine phosphate (10 mmol/l) was added to the cardioplegic solution, six out of seven animals could be weaned from bypass and the heart performance assessed by volume loading. Group II also exhibited better maintenance of high-energy phosphates during ischemia, with significantly higher adenylate charge potential, than group I. In all animals weaned from bypass--two in group I and six in group II--the ventricular performance was decreased compared with that before induction of ischemia. The results indicate that creatine phosphate could be an effective constituent in potassium cardioplegia.

show abstract

Creatine phosphate: An additive myocardial protective and antiarrhythmic agent in cardioplegia

Cited by 80 publications

References 39 publications

Effect of ATP synthesis promoters on postischemic myocardial recovery

Effect of ATP synthesis promoters on postischemic myocardial recovery

Biochemical and Functional Effects of Creatine Phosphate in Cardioplegic Solution during Aortic Valve Surgery - a Clinical Study

Improved Myocardial Protection by Creatine Phosphate in Cardioplegic Solution. An In Vivo Study in the Pig During Normothermic Ischemia

Contact Info

Product

Resources

About