Advantages of continuous hyperpolarized arrest with pinacidil over St. Thomas' hospital solution during prolonged ischemia

Jayawant, Mark; Stephenson, Edward R.; Damiano, Ralph J.

doi:10.1016/s0022-5223(98)70251-x

Cited by 15 publications

(8 citation statements)

References 22 publications

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“…These potassium-channel openers have been shown to be superior or equivalent to depolarized arrest during both short and long periods of global ischemia. [5][6][7] Other laboratories have corroborated our findings that hyperpolarized arrest may be superior to depolarized arrest for myocardial protection. 8,9 Recently, we have shown that ATP-sensitive potassium-channel openers prevent intracellular calcium accumulation during global ischemia.…”

supporting

confidence: 83%

“…Our laboratory has proposed that adopting an alternative strategy of hyperpolarized arrest may alleviate many of these untoward sequelae. [5][6][7] To hyperpolarize the cell membrane, we have administered drugs that open ATP-sensitive potassium channels. These potassium-channel openers have been shown to be superior or equivalent to depolarized arrest during both short and long periods of global ischemia.…”

mentioning

confidence: 99%

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Donor heart preservation with a novel hyperpolarizing solution: Superior protection compared with University of Wisconsin solution

Hoenicke

Sun

Strange

et al. 2000

The Journal of Thoracic and Cardiovascular Surgery

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Extending donor heart preservation time would offer several advantages. Surgical results would likely improve because it has been demonstrated with present solutions that cold ischemic times inversely correlate with postoperative survival. 1 It also would allow for O ne of the most significant limitations in heart transplantation is the relatively short preservation time that current preservation solutions offer. Safe organ preservation can be maintained for only 4 hours.Objectives: A donor heart preservation solution was designed to use hyperpolarized arrest with the adenosine triphosphate-sensitive potassium-channel opener pinacidil. This solution contained concentrations of potassium, sodium, calcium, magnesium, lactobionate, and the buffer histidine specifically chosen to minimize intracellular calcium accumulation associated with prolonged ischemia.Methods: Twenty-four rabbit hearts were randomly assigned to receive 1 of 3 preservation solutions in a crystalloid-perfused Langendorff model: (1) prototype solution containing a 0.5 mmol/L concentration of pinacidil, (2) prototype solution without pinacidil as control, and (3) University of Wisconsin solution. Thirty minutes of initial perfusion preceded baseline data acquisition. Data comprised left ventricle pressure-volume curves generated by inflating an intraventricular latex balloon. After cardioplegic administration, hearts underwent 4 hours of hypothermic storage, followed by 60 minutes of reperfusion and postischemic data acquisition.Results: Postischemic developed pressure was better preserved by pinacidil solution (92.4% ± 4.5%) than by the control (74.9% ± 3.4%, P = .01) and University of Wisconsin solutions (66.7% ± 5.1%, P = .001). Diastolic negative dP/dT was better preserved by pinacidil solution (104.4% ± 10.2%) than by the control (80.2% ± 4.2%, P = .034) and University of Wisconsin solutions (71.7% ± 7.0%, P = .015). Diastolic compliance, expressed as baseline/postischemic diastolic slope ratios, was more poorly preserved by University of Wisconsin solution (0.67 ± 0.07) than by the pinacidil (0.88 ± 0.05, P = .041) and control solutions (0.87 ± 0.05, P = .021). Postischemic coronary flow was higher in hearts exposed to pinacidil solution (77.8% ± 3.0%) than in those exposed to the control (66.8% ± 2.4%) and University of Wisconsin solutions (70.9% ± 4.0%, P = .07). Conclusions:The superiority of the pinacidil solution in this experiment demonstrated that hyperpolarized arrest with potassium-channel openers improves donor heart preservation when administered in a novel histidinebuffered lactobionate-enriched vehicle.

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supporting

confidence: 83%

mentioning

confidence: 99%

Donor heart preservation with a novel hyperpolarizing solution: Superior protection compared with University of Wisconsin solution

Hoenicke

Sun

Strange

et al. 2000

The Journal of Thoracic and Cardiovascular Surgery

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“…Although this blood-perfused model offers a closer approximation to the clinical scenario than a crystalloid perfused one, care should be taken in extrapolating results from the present study to the clinical setting, as shown in a blood-perfused, parabiotic, isolated rabbit heart model (6,7,9,15). To determine the clinical feasibility of nicorandil cardioplegia, in vivo studies are clearly needed.…”

Section: Discussionmentioning

confidence: 98%

Left ventricular mechanoenergetics after hyperpolarized cardioplegic arrest by nicorandil and after depolarized cardioplegic arrest by KCl

Kobayashi¹,

Yoshikawa²,

Satoh³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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We hypothesized that there are no differences in left ventricular (LV) mechanoenergetics between after hyperpolarized cardioplegic arrest by nicorandil (nicorandil arrest) and after depolarized one by high potassium chloride (KCl arrest). The aim of the present study was to test this hypothesis using LV curved end-systolic pressure-volume relation (ESPVR) and linear pressure-volume area (PVA)-myocardial oxygen consumption per beat (VO2) relation. All hearts underwent 30 min global ischemia (30 degrees C) after infusion of 5 ml of cardioplegia. Cardioplegia consisted of either 30 mmol/l KCl (7 hearts) or nicorandil (100 micromol/l) in Tyrode solution (6 hearts). After a 30-min blood reperfusion, ESPVR and VO2-PVA relation were assessed again. Mean end-systolic pressure (ESP(mLVV)) and mean PVA at midrange LV volume (PVA(mLVV)) significantly (P < 0.05) decreased to 79.1 +/- 13.4% and 85.4 +/- 17.1% of control after KCl arrest and to 85.3 +/- 14.8% and 86.4 +/- 16.9% of control after nicorandil arrest. There were no significant differences in both decreases of mean ESP(mLVV) and PVA(mLVV) between each arrest. The slopes of VO2-PVA relations were also unchanged after each arrest. There was a significant (P < 0.005) difference in the decreases of mean VO2 intercepts of VO2-PVA relations between post-KCl arrest (73.9 +/- 8.2% of control) and post-nicorandil arrest (99.2 +/- 10.1% of control), however. Proteolysis of alpha-fodrin due to Ca2+ overload was significantly marked after KCl arrest. The present results indicate that the total calcium handling in excitation-contraction coupling is transiently impaired after KCl arrest, whereas it is unchanged after nicorandil arrest. This suggests the possibility that nicorandil is a better cardioplegia than KCl.

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“…This process was proposed as a preservation of energy. 6 PCOs have been shown to reduce infarct size, attenuate myocardial stunning, and ameliorate reperfusion injury. 7 Another advantage of PCOs may be their ability to prevent the cell swelling which has been implicated as a cause in ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

Myocardial protective effects of nicorandil, an opener of potassium channels on senile rat heart

Liu

Long

Ji³

et al. 2006

Perfusion

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The purpose of this study was to investigate the cardioprotective effects of nicorandil, an opener of potassium channels, on senile rat hearts from ischemic reperfusion injury. A modified working model of isolated perfused hearts of senile rats was used. After isolation, the hearts underwent 60 min of global hypothermic ischemia treatment, followed by 30 min of reperfusion. These hearts were distributed into three groups, each receiving different cardioplegic solutions: (1) St. Thomas' solution (Group S), (2) 100 micromol/L nicorandil (Group N), (3) St. Thomas' solution combined with 100 micromol/L nicorandil (Group S+N). The pre- and post-ischemic myocardial function were assessed by the percentage recovery of the heart rate (HR), +/- dp/dt(max) (maximal rate of change of left ventricular pressure) and cardiac output (CO). Upon reperfusion, the cardioplegic solution was collected from the coronary sinus and tested for lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity. During 30 min of reperfusion, the percentage recovery of HR, +dp/dt and left ventricular stroke work (LVSW) were significantly higher in Group S+N than in Group S and Group N (p < 0.05). The percentage of recovery in CO was higher in Group N and Group S+N than in Group S. The electrical activities arresting time (EAT) and mechanical activities arresting time (MAT) were longer in Group N than in Group S and Group N+S (p < 0.01). There were no statistical significance between Group S and Group N+S (p > 0.05). There were no significant differences in the levels of LDH and CK-MB. Electron microscopic examination revealed better preservation of the ultrastructures of the myocardial tissue in Group N+S than the other two groups. These results indicate that nicorandil combined with St. Thomas' solution can improve the left ventricular function of the post-ischemic senile rat and offer a better myocardial protective effect on the ischemic senile myocardium.

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Advantages of continuous hyperpolarized arrest with pinacidil over St. Thomas' hospital solution during prolonged ischemia

Cited by 15 publications

References 22 publications

Donor heart preservation with a novel hyperpolarizing solution: Superior protection compared with University of Wisconsin solution

Donor heart preservation with a novel hyperpolarizing solution: Superior protection compared with University of Wisconsin solution

Left ventricular mechanoenergetics after hyperpolarized cardioplegic arrest by nicorandil and after depolarized cardioplegic arrest by KCl

Myocardial protective effects of nicorandil, an opener of potassium channels on senile rat heart

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